BRCA2

Summary

Gene Symbol: BRCA2
Description: BRCA2, DNA repair associated
Alias: BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD, FANCD1, GLM3, PNCA2, XRCC11, breast cancer type 2 susceptibility protein, BRCA1/BRCA2-containing complex, subunit 2, Fanconi anemia group D1 protein, breast and ovarian cancer susceptibility gene, early onset, breast and ovarian cancer susceptibility protein 2, breast cancer 2 tumor suppressor, breast cancer 2, early onset, mutant BRCA2, truncated breast cancer 2
Species: human

Top Publications

  1. pmc Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies
    A Antoniou
    Cancer Research U K Genetic Epidemiology Unit, Department of Public Health, University of Cambridge, Cambridge, United Kingdom
    Am J Hum Genet 72:1117-30. 2003
  2. ncbi Biallelic inactivation of BRCA2 in Fanconi anemia
    Niall G Howlett
    Department of Pediatric Oncology, Children s Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Science 297:606-9. 2002
  3. pmc Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11
    Katharina Schlacher
    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 145:529-42. 2011
  4. pmc Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2
    Anna Marie Mulligan
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Worts Causeway, Cambridge, CB1 8RN, UK
    Breast Cancer Res 13:R110. 2011
  5. pmc Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
    Antonis C Antoniou
    Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
    Hum Mol Genet 20:3304-21. 2011
  6. pmc The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA
    Tina Thorslund
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire, UK
    Nat Struct Mol Biol 17:1263-5. 2010
  7. ncbi Insights into DNA recombination from the structure of a RAD51-BRCA2 complex
    Luca Pellegrini
    University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge CB2 1GA, UK
    Nature 420:287-93. 2002
  8. ncbi Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer
    William D Foulkes
    Program in Cancer Genetics, Department of Oncology and Human Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
    J Natl Cancer Inst 95:1482-5. 2003
  9. ncbi Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years
    Kathleen E Malone
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cancer Res 66:8297-308. 2006
  10. pmc Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes
    Roger A Greenberg
    Department of Genetics, Harvard Medical School and the Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 20:34-46. 2006

Research Grants

  1. Obesity susceptibility loci and breast cancer risk in BRCA1 and BRCA2 mutation ca
    JONATHAN ANDREW MITCHELL; Fiscal Year: 2013
  2. Wei Zheng; Fiscal Year: 2015
  3. ERICA LYNN CAIN; Fiscal Year: 2014
  4. Simon N Powell; Fiscal Year: 2016
  5. PHENOTYPIC RISK MARKERS IN BRCA1 MUTATION CARRIERS
    Gail Tomlinson; Fiscal Year: 2002
  6. Mechanisms of Carcinogenesis in BRCA2 Mutant Cells
    Jeffrey Holt; Fiscal Year: 2005
  7. ROLES OF BRCA1 AND BRCA2 IN BREAST CARCINOGENESIS
    Daniel Silver; Fiscal Year: 2003
  8. Mechanistic Studies of BRCA2-RAD51 Mediated DNA Repair
    Erika Brown; Fiscal Year: 2006
  9. Early Detection of Pancreatic Cancer Using Ice COLD-PCR
    Grant Wu; Fiscal Year: 2012
  10. Rahul Nene; Fiscal Year: 2015

Detail Information

Publications365 found, 100 shown here

  1. pmc Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies
    A Antoniou
    Cancer Research U K Genetic Epidemiology Unit, Department of Public Health, University of Cambridge, Cambridge, United Kingdom
    Am J Hum Genet 72:1117-30. 2003
    Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context...
  2. ncbi Biallelic inactivation of BRCA2 in Fanconi anemia
    Niall G Howlett
    Department of Pediatric Oncology, Children s Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Science 297:606-9. 2002
    ..Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins...
  3. pmc Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11
    Katharina Schlacher
    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 145:529-42. 2011
    Breast cancer suppressor BRCA2 is critical for maintenance of genomic integrity and resistance to agents that damage DNA or collapse replication forks, presumably through homology-directed repair of double-strand breaks (HDR)...
  4. pmc Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2
    Anna Marie Mulligan
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Worts Causeway, Cambridge, CB1 8RN, UK
    Breast Cancer Res 13:R110. 2011
    ..common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers...
  5. pmc Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
    Antonis C Antoniou
    Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
    Hum Mol Genet 20:3304-21. 2011
    ..breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently ..
  6. pmc The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA
    Tina Thorslund
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire, UK
    Nat Struct Mol Biol 17:1263-5. 2010
    Individuals with BRCA2 mutations are predisposed to breast cancers owing to genome instability. To determine the functions of BRCA2, the human protein was purified...
  7. ncbi Insights into DNA recombination from the structure of a RAD51-BRCA2 complex
    Luca Pellegrini
    University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge CB2 1GA, UK
    Nature 420:287-93. 2002
    The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination...
  8. ncbi Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer
    William D Foulkes
    Program in Cancer Genetics, Department of Oncology and Human Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
    J Natl Cancer Inst 95:1482-5. 2003
    ..Among 292 breast cancer specimens previously analyzed for ER, erbB-2, p53, and germline mutations in BRCA1 and BRCA2, we identified 76 that did not overexpress ER or erbB-2...
  9. ncbi Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years
    Kathleen E Malone
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cancer Res 66:8297-308. 2006
    Although well studied in families at high-risk, the roles of mutations in the BRCA1 and BRCA2 genes are poorly understood in breast cancers in the general population, particularly in Black women and in age groups outside of the very ..
  10. pmc Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes
    Roger A Greenberg
    Department of Genetics, Harvard Medical School and the Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 20:34-46. 2006
    ..The results support a new, multifactorial model that describes how genotoxic stress enables BRCA1 to execute a diverse set of DNA damage-response functions...
  11. doi A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients
    David J Sanz
    Grupo de Genetica del Cancer, Instituto de Biologia y Genetica Molecular, Consejo Superior de Investigaciones Cientificas Universidad de Valladolid, Valladolid, Spain
    Clin Cancer Res 16:1957-67. 2010
    ..An increasing amount of evidence indicates that there can be deleterious effects through the disruption of the splicing process. We have investigated the effect of aberrant splicing of BRCA1/2 on hereditary breast/ovarian cancer (HBOC)...
  12. ncbi Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2
    Bing Xia
    Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    Mol Cell 22:719-29. 2006
    b>BRCA2 mutations predispose carriers to breast and ovarian cancer and can also cause other cancers and Fanconi anemia...
  13. ncbi Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations
    James D Fackenthal
    Department of Medicine and Center for Clinical Cancer Genetics, University of Chicago, Box MC2115, 5841 S Maryland Avenue, Chicago, Illinois 60615, USA
    Nat Rev Cancer 7:937-48. 2007
    Germline mutations in the BRCA1 or BRCA2 tumour-suppressor genes are strong predictors of breast and/or ovarian cancer development...
  14. ncbi Identification of the breast cancer susceptibility gene BRCA2
    R Wooster
    Section of Molecular Carcinogenesis, Haddow Laboratories, Sutton Surrey, UK
    Nature 378:789-92. 1995
    ..The breast cancer susceptibility gene, BRCA2, was recently localized to chromosome 13q12-q13...
  15. pmc Unraveling the mechanism of BRCA2 in homologous recombination
    William K Holloman
    Department of Microbiology and Immunology, Weill Cornell Cancer Center, Weill Cornell Medical College, New York, New York, USA
    Nat Struct Mol Biol 18:748-54. 2011
    b>BRCA2 is the product of a breast cancer susceptibility gene in humans and the founding member of an emerging family of proteins present throughout the eukaryotic domain that serve in homologous recombination...
  16. pmc The carboxyl terminus of Brca2 links the disassembly of Rad51 complexes to mitotic entry
    Nabieh Ayoub
    Medical Research Council Cancer Cell Unit, Hutchison MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK
    Curr Biol 19:1075-85. 2009
    ..Rad51 assembly is regulated by the breast cancer suppressor Brca2, via its evolutionarily conserved BRC repeats, and a distinct carboxy (C)-terminal motif whose biological function ..
  17. pmc BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage
    Alan R Schoenfeld
    Derald H Ruttenberg Cancer Center, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1130, New York, NY 10029, USA
    Mol Cell Biol 24:7444-55. 2004
    Individuals carrying a germ line mutation of the breast cancer susceptibility gene BRCA2 are predisposed to breast, ovarian, and other types of cancer...
  18. pmc Long-term ovarian cancer survival associated with mutation in BRCA1 or BRCA2
    John R McLaughlin
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
    J Natl Cancer Inst 105:141-8. 2013
    Studies have suggested that the 5-year survival of women with ovarian cancer and a BRCA1 or BRCA2 mutation is better than expected...
  19. ncbi BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated risks to relatives
    Fiona Lalloo
    Department of Clinical, Genetics and Academic Unit of Medical Genetics, St Mary s Hospital, Hathersage Road, Manchester M13 0JH, United Kingdom
    Eur J Cancer 42:1143-50. 2006
    Pathological mutations in BRCA1, BRCA2 and TP53 are associated with an increased risk of breast cancer...
  20. ncbi BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model
    Kristen J Vogel
    Center for Medical Genetics, Evanston Northwestern Healthcare, Evanston, IL, USA
    J Clin Oncol 25:4635-41. 2007
    The BRCAPRO model, used to predict a family's likelihood of carrying a BRCA1 or BRCA2 mutation, was designed using mutation frequencies of white and Ashkenazi Jewish populations, and may not be applicable to other populations...
  21. pmc The prevalence of BRCA1 mutations among young women with triple-negative breast cancer
    S R Young
    Women s College Research Institute, Department of Public Health, The University of Toronto, Toronto, Canada
    BMC Cancer 9:86. 2009
    Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer...
  22. doi Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups
    B G Haffty
    Department of Radiation Oncology, UMDNJ RWJMS and Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA
    Ann Oncol 20:1653-9. 2009
    ..The purpose of this study is to evaluate the prevalence of BRCA1/2 mutations and the association between BRCA1/2 mutation status and secondary malignancies among young women with breast cancer in these three racially diverse groups...
  23. doi Preventing future cancers by testing women with ovarian cancer for BRCA mutations
    Janice S Kwon
    Division of Gynecologic Oncology, University of British Columbia, British Columbia, Canada
    J Clin Oncol 28:675-82. 2010
    ..We estimated the net health benefits and cost-effectiveness of different criteria for BRCA mutation testing in women with ovarian cancer, and the downstream benefits for their first-degree relatives (FDRs)...
  24. doi Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2
    Nancie Petrucelli
    Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA
    Genet Med 12:245-59. 2010
    Hereditary breast and ovarian cancer due to mutations in the BRCA1 and BRCA2 genes is the most common cause of hereditary forms of both breast and ovarian cancer...
  25. pmc Prevalence of the variant allele rs61764370 T>G in the 3'UTR of KRAS among Dutch BRCA1, BRCA2 and non-BRCA1/BRCA2 breast cancer families
    Antoinette Hollestelle
    Department of Medical Oncology, Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Erasmus University Medical Center, Rotterdam, The Netherlands
    Breast Cancer Res Treat 128:79-84. 2011
    ..In the current study, we have genotyped this KRAS-variant in breast cancer index cases from 268 BRCA1 families, 89 BRCA2 families, 685 non-BRCA1/BRCA2 families, and 797 geographically matched controls...
  26. doi Assessing the RNA effect of 26 DNA variants in the BRCA1 and BRCA2 genes
    Mireia Menendez
    Hereditary Cancer Program, Genetic Diagnosis Unit, Laboratori de Recerca Translacional, Institut Catala d Oncologia, Hospital Duran i Reynals Bellvitge Biomedical Research Institute, L Hospitalet de Llobregat, Barcelona and Hospital Josep Trueta, IdiBGi, Gran Via 199 203, Girona 08908, Spain
    Breast Cancer Res Treat 132:979-92. 2012
    Comprehensive genetic testing of the breast cancer susceptibility genes BRCA1 and BRCA2 identified approximately 16% of variants of unknown significance (VUS), a significant proportion of which could affect the correct splicing of the ..
  27. ncbi Mutation analysis in the BRCA2 gene in primary breast cancers
    Y Miki
    Department of Human Genome Analysis, Cancer Chemotherapy Center, Tokyo, Japan
    Nat Genet 13:245-7. 1996
    ..1), BRCA2 (ref. 2), TP53 (ref...
  28. pmc Somatic mutations in BRCA1 and BRCA2 could expand the number of patients that benefit from poly (ADP ribose) polymerase inhibitors in ovarian cancer
    Bryan T J Hennessy
    Department of Gynecology Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 28:3570-6. 2010
    ..3%. It is important to determine the frequency of somatic BRCA(1/2) changes, given the sensitivity of BRCA-mutated cancers to poly (ADP ribose) polymerase-1 (PARP1) inhibitors and platinum analogs...
  29. pmc Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in Pakistan
    Alexander Liede
    University of Toronto, Sunnybrook and Women s College Health Sciences Centre, Toronto, Ontario, Canada
    Am J Hum Genet 71:595-606. 2002
    ..The prevalence of BRCA1 or BRCA2 mutations among case subjects with breast cancer was 6.7% (95% confidence interval [CI] 4.1%-9...
  30. ncbi BRCA2 germline mutations in familial pancreatic carcinoma
    Stephan A Hahn
    Department of Internal Medicine, Knappschaftskrankenhaus University of Bochum, Germany
    J Natl Cancer Inst 95:214-21. 2003
    ..Some studies have shown that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer...
  31. pmc Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2
    Blanche P Alter
    Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Executive Plaza South, Room 7020, Rockville, MD 20852 7231, USA
    J Med Genet 44:1-9. 2007
    Patients with biallelic mutations in BRCA2 are in Fanconi anaemia group D1...
  32. pmc Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer
    E Thirthagiri
    Cancer Research Initiatives Foundation, Subang Jaya Medical Centre, Kuala Lumpur, Malaysia
    Breast Cancer Res 10:R59. 2008
    The cost of genetic testing and the limited knowledge about the BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia...
  33. pmc Incorporating tumour pathology information into breast cancer risk prediction algorithms
    Nasim Mavaddat
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK
    Breast Cancer Res 12:R28. 2010
    Mutations in BRCA1 and BRCA2 confer high risks of breast cancer and ovarian cancer...
  34. doi Expanding the criteria for BRCA mutation testing in breast cancer survivors
    Janice S Kwon
    Division of Gynecologic Oncology, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    J Clin Oncol 28:4214-20. 2010
    ..Not all potential carriers are identified by existing criteria for BRCA testing. We estimated the costs and benefits of different BRCA testing criteria for women with breast cancer younger than 50 years...
  35. ncbi Improved survival in women with BRCA-associated ovarian carcinoma
    Ilana Cass
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars Sinai Medical Center and University of California Los Angeles School of Medicine, Los Angeles, California 90048, USAA
    Cancer 97:2187-95. 2003
    ..The objective of this study was to determine the clinical characteristics, treatment response, and frequency of p53 overexpression in Ashkenazi Jewish women with hereditary ovarian carcinoma...
  36. ncbi Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2
    Mary Claire King
    Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Science 302:643-6. 2003
    ..cancer were determined for Ashkenazi Jewish women with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2. We selected 1008 index cases, regardless of family history of cancer, and carried out molecular analysis across ..
  37. pmc A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes
    Douglas F Easton
    Genetic Epidemiology Unit, Strangeways Research Laboratories, University of Cambridge, Cambridge, UK
    Am J Hum Genet 81:873-83. 2007
    Mutation screening of the breast and ovarian cancer-predisposition genes BRCA1 and BRCA2 is becoming an increasingly important part of clinical practice...
  38. pmc Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination
    Rémi Buisson
    Genome Stability Laboratory, Laval University Cancer Research Center, Hotel Dieu de Quebec, Quebec City, Quebec, Canada
    Nat Struct Mol Biol 17:1247-54. 2010
    ..PALB2's tumor-suppressing effect is thought to be based on its ability to facilitate BRCA2's function in homologous recombination. However, the biochemical properties of PALB2 are unknown...
  39. pmc BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients
    Z Kote-Jarai
    Oncogenetics team, The Institute of Cancer Research, Sutton SM2 5NG, UK
    Br J Cancer 105:1230-4. 2011
    ..We previously estimated that about 2% of PrCa cases diagnosed ≤ 55 years harbour a BRCA2 mutation and PrCa among BRCA2 carriers has been shown to be more aggressive, with poorer survival.
  40. ncbi CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair
    Fumiko Esashi
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 434:598-604. 2005
    Inherited mutations in BRCA2 are associated with a predisposition to early-onset breast cancers. The underlying basis of tumorigenesis is thought to be linked to defects in DNA double-strand break repair by homologous recombination...
  41. pmc Familial clustering of site-specific cancer risks associated with BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population
    Sharon Simchoni
    Medical Genetics Unit, Shaare Zedek Medical Center, Hebrew University Medical School, Jerusalem 91031, Israel
    Proc Natl Acad Sci U S A 103:3770-4. 2006
    Inherited mutations in BRCA1 and BRCA2 lead to significantly increased risks of breast and ovarian cancer. We used epidemiologic methods to evaluate the relative risks of breast cancer vs...
  42. pmc Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers
    Xianshu Wang
    Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
    Hum Mol Genet 19:2886-97. 2010
    ..have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers...
  43. pmc A region of human BRCA2 containing multiple BRC repeats promotes RAD51-mediated strand exchange
    Mahmud K K Shivji
    Cancer Research UK Department of Oncology and The Medical Research Council Cancer Cell Unit, Hutchison MRC Research Centre, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK
    Nucleic Acids Res 34:4000-11. 2006
    Human BRCA2, a breast and ovarian cancer suppressor, binds to the DNA recombinase RAD51 through eight conserved BRC repeats, motifs of approximately 30 residues, dispersed across a large region of the protein...
  44. ncbi BRCA2 associates with acetyltransferase activity when bound to P/CAF
    F Fuks
    Wellcome CRC Institute and Department of Pathology, Cambridge University, UK
    Oncogene 17:2531-4. 1998
    Predisposition to hereditary breast cancer has been attributed in part to inherited mutations in the BRCA2 gene. The large protein it encodes is still poorly characterized with respect to functions...
  45. ncbi Survival of breast cancer patients in BRCA1, BRCA2, and non-BRCA1/2 breast cancer families: a relative survival analysis from Finland
    H Eerola
    Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
    Int J Cancer 93:368-72. 2001
    ..survival rates of 359 familial breast cancer patients (32 patients from BRCA1-positive families, 43 patients from BRCA2-positive families and 284 patients from BRCA1/2-negative breast cancer families) and compared them with those of ..
  46. ncbi Population attributes affecting the prevalence of BRCA mutation carriers in epithelial ovarian cancer cases in israel
    G Hirsh-Yechezkel
    Cancer Epidemiology Unit, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, Israel
    Gynecol Oncol 89:494-8. 2003
    ..The objective was to evaluate the prevalence of BRCA1/2 mutations in selected categories of ovarian cancer patients in Israel...
  47. ncbi Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer
    Robert M Wenham
    Department of Obstetrics and Gynecology Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Clin Cancer Res 9:4396-403. 2003
    Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles...
  48. pmc Association of NQO1 polymorphism with spontaneous breast cancer in two independent populations
    H J Menzel
    Inst f med Biology and Human Genetics, University Innsbruck, Schopfstrasse 41, A 6020 Innsbruck, Austria
    Br J Cancer 90:1989-94. 2004
    ..Six SNPs, Q356R and P871L in BRCA1, N372H in BRCA2, C112R (E4) and R158C (E2) in ApoE and C825T in GNB3, did not show any sign of association...
  49. ncbi Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers
    H Jernstrom
    Jubileum Institute, Department of Oncology, Lund University Hospital, Lund, Sweden
    J Natl Cancer Inst 96:1094-8. 2004
    ..Whether breast-feeding is associated with a reduced risk of hereditary breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations is currently unknown.
  50. ncbi Increased prevalence of the BRCA2 polymorphic stop codon K3326X among individuals with familial pancreatic cancer
    Sean T Martin
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21205 2196, USA
    Oncogene 24:3652-6. 2005
    Germline BRCA2 mutations predispose to the development of pancreatic cancer...
  51. pmc Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family
    D Gareth Evans
    Academic Unit of Medical Genetics and Regional Genetics Service, St Mary s Hospital Manchester M13 0JH, UK
    BMC Cancer 8:155. 2008
    The identification of a BRCA1 or BRCA2 mutation in familial breast cancer kindreds allows genetic testing of at risk relatives...
  52. pmc BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer
    Michael J Hall
    Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA
    Cancer 115:2222-33. 2009
    ..increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (BRCA1) and BRCA2 has important implications for screening and prevention counseling...
  53. doi BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients
    Myong Cheol Lim
    Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, 111, Jungbalsan ro, Ilsandong gu, Goyang si, Gyeonggi do 410 769, Korea
    J Cancer Res Clin Oncol 135:1593-9. 2009
    ..To evaluate the proportion of Korean ovarian cancer patients with a strong family history and the genetic status in such patients...
  54. doi Low contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer in the Korean population
    Moon Woo Seong
    Department of Laboratory Medicine, Seoul National University Hospital and Clinical Research Institute, Chongno Gu, Seoul 110 744, Korea
    Fam Cancer 8:505-8. 2009
    ..BRCA1/2 genomic rearrangement, however, is likely to make only a small contribution to breast cancer in this population...
  55. pmc A mitotic function for the high-mobility group protein HMG20b regulated by its interaction with the BRC repeats of the BRCA2 tumor suppressor
    M Lee
    Department of Oncology and The Medical Research Council Cancer Cell Unit, Hutchison MRC Research Centre, University of Cambridge, Cambridge, UK
    Oncogene 30:3360-9. 2011
    The inactivation of BRCA2, a suppressor of breast, ovarian and other epithelial cancers, triggers instability in chromosome structure and number, which are thought to arise from defects in DNA recombination and mitotic cell division, ..
  56. doi Tetraploidy in BRCA2 breast tumours
    Asta Björk Jonsdottir
    Cancer Research Laboratory, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
    Eur J Cancer 48:305-10. 2012
    ..We have recently reported delayed cytokinesis in primary human fibroblasts from BRCA2 mutation carriers, implying a function for the BRCA2 tumour suppressor in completion of cell division...
  57. pmc Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer
    Kelly L Bolton
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
    JAMA 307:382-90. 2012
    ..10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of ..
  58. pmc Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival
    Joyce Liu
    Department of Medical Oncology, Dana Farber Partners CancerCare, Boston, MA, USA
    Cancer Genet 205:34-41. 2012
    ..examined clinical characteristics, including event-free survival (EFS) and overall survival (OS), for BRCA1 versus BRCA2 patients. We identified 197 cases (148 BRCA1 cases; 49 BRCA2 cases); the median follow-up period was 63 months...
  59. doi Unravelling modifiers of breast and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: update on genetic modifiers
    D R Barnes
    Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
    J Intern Med 271:331-43. 2012
    Pathogenic mutations in the tumour suppressor genes BRCA1 and BRCA2 confer increased risks for breast and ovarian cancer and account for approximately 15% of the excess familial risk of breast cancer amongst first-degree relatives of ..
  60. doi High levels of wild-type BRCA2 suppress homologous recombination
    Alissa C Magwood
    Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1
    J Mol Biol 421:38-53. 2012
    Endogenous levels of the BRCA2 (breast cancer susceptibility 2) protein promote homologous recombination by regulating the essential strand exchange protein RAD51...
  61. pmc Outcomes of primary surgical cytoreduction in patients with BRCA-associated high-grade serous ovarian carcinoma
    David M Hyman
    Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 E 66th Street, New York, NY 10065, USA
    Gynecol Oncol 126:224-8. 2012
    ..BRCA-associated and sporadic ovarian cancers have different pathologic and clinical features. Our goal was to determine if BRCA mutation status is an independent predictor of residual tumor volume following primary surgical cytoreduction...
  62. pmc Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes
    Alberto Acedo
    Grupo de Splicing y Cáncer, Instituto de Biología y Genética Molecular IBGM, Consejo Superior de Investigaciones Científicas CSIC Universidad de Valladolid, Sanz y Forés 3, Valladolid 47003, Spain
    Breast Cancer Res 14:R87. 2012
    ..We aimed to investigate the effect on splicing of the BRCA2 variants c.8488-1G > A (exon 20) and c...
  63. doi High grade prostatic intraepithelial neoplasia does not display loss of heterozygosity at the mutation locus in BRCA2 mutation carriers with aggressive prostate cancer
    Amber Willems-Jones
    Kathleen Cuningham Consortium for Research into Familial Breast Cancer, kConFab, Research Department, Peter MacCallum Cancer Centre, East Melbourne, Australia
    BJU Int 110:E1181-6. 2012
    ..The risk of developing aggressive prostate cancer is increased for men carrying a pathogenic germline mutation in BRCA2. An earlier study by the Kathleen Cuningham Consortium for Research into Familial Breast Cancer showed that BRCA2 ..
  64. pmc Whole exome sequencing suggests much of non-BRCA1/BRCA2 familial breast cancer is due to moderate and low penetrance susceptibility alleles
    Francisco Javier Gracia-Aznárez
    Human Genetics Group, Spanish National Cancer Centre CNIO, Madrid, Spain
    PLoS ONE 8:e55681. 2013
    The identification of the two most prevalent susceptibility genes in breast cancer, BRCA1 and BRCA2, was the beginning of a sustained effort to uncover new genes explaining the missing heritability in this disease...
  65. pmc Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain)
    Pilar Blay
    Unidad de Cáncer Familiar, Servicio de Oncologia Medica, Instituto Universitario de Oncologia del Principado de Asturias IUOPA, Hospital Universitario Central de Asturias HUCA, Calle de Celestino Villamil, Oviedo 33006, Spain
    BMC Cancer 13:243. 2013
    The prevalence of BRCA1 and BRCA2 mutations in Spain is heterogeneous and varies according to geographical origin of studied families...
  66. pmc Age-dependent penetrance of different germline mutations in the BRCA1 gene
    F Al-Mulla
    Department of Pathology, Safat, Kuwait
    J Clin Pathol 62:350-6. 2009
    ..This study addresses whether different exon mutations have variable expressivity especially in relation to the age of onset of breast cancer...
  67. pmc MRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks
    Tomohiro Hayakawa
    Laboratory for Chromatin Dynamics, RIKEN Center for Developmental Biology, Kobe, Hyogo 650 0047, Japan
    J Cell Sci 123:1124-30. 2010
    PALB2 physically and functionally connects the proteins encoded by the BRCA1 and BRCA2 breast and ovarian cancer genes into a DNA-damage-response network...
  68. ncbi Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2
    B B Roa
    Baylor DNA Diagnostic Laboratory, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Genet 14:185-7. 1996
    BRCA1 and BRCA2 are the two major identified causes of inherited breast cancer, with mutations in either gene conferring up to 80-90% lifetime risk of breast cancer in carrier females...
  69. ncbi Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan
    S S Li
    Institute of Biomedical Sciences, National Sun Yat Sen University, Kaohsiung, Taiwan, Republic of China
    Hum Genet 104:201-4. 1999
    ..southern Taiwan, and 5 of these families were found to carry cancer-associated germline mutations in the BRCA1 and BRCA2 genes...
  70. ncbi Frequency of BRCA1 and BRCA2 mutations in unselected Ashkenazi Jewish patients with colorectal cancer
    Tomas Kirchhoff
    Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Natl Cancer Inst 96:68-70. 2004
    Mutations in BRCA1 and BRCA2 that predispose to breast and ovarian cancer are detected in approximately 2.5% of the Ashkenazi Jewish population...
  71. ncbi Germline mutations in BRCA2: shared genetic susceptibility to breast cancer, early onset leukemia, and Fanconi anemia
    John E Wagner
    Division of Pediatric Hematology, Oncology, and Blood Marrow Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA
    Blood 103:3226-9. 2004
    ..breast cancer susceptibility gene BRCA2 has recently been identified as identical to the Fanconi anemia (FA) gene FANCD1. Here we expand the clinical implications of this discovery...
  72. ncbi Prevalence of BRCA1 and BRCA2 mutations in women diagnosed with ductal carcinoma in situ
    Elizabeth B Claus
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn 06520 8034, USA
    JAMA 293:964-9. 2005
    The distribution of BRCA1 and BRCA2 mutations in women diagnosed with noninvasive breast carcinoma is unknown.
  73. pmc Expression profiling of familial breast cancers demonstrates higher expression of FGFR2 in BRCA2-associated tumors
    Anita L Bane
    Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
    Breast Cancer Res Treat 117:183-91. 2009
    BRCA1- and BRCA2-associated tumors appear to have distinct molecular signatures. BRCA1-associated tumors are predominantly basal-like cancers, whereas BRCA2-associated tumors have a predominant luminal-like phenotype...
  74. pmc PALB2 links BRCA1 and BRCA2 in the DNA-damage response
    Feng Zhang
    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 1520, Ann Arbor, MI 48109, USA
    Curr Biol 19:524-9. 2009
    BRCA1 and BRCA2 are often mutated in familial breast and ovarian cancer. Both tumor suppressors play key roles in the DNA-damage response...
  75. pmc Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
    Phillip J Whiley
    School of Chemistry and Molecular Biosciences, The University of Queensland, Australia
    BMC Med Genet 11:80. 2010
    ..a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although ..
  76. pmc The occurrence of germline BRCA1 and BRCA2 sequence alterations in Slovenian population
    Vida Stegel
    Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia
    BMC Med Genet 12:9. 2011
    the BRCA1 and BRCA2 mutation spectrum and mutation detection rates according to different family histories were investigated in 521 subjects from 322 unrelated Slovenian cancer families with breast and/or ovarian cancer.
  77. ncbi RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2
    A K Wong
    Myriad Genetics, Inc, Salt Lake City, Utah 84108, USA
    J Biol Chem 272:31941-4. 1997
    Recent work has shown that the murine BRCA2 tumor suppressor protein interacts with the murine RAD51 protein. This interaction suggests that BRCA2 participates in DNA repair...
  78. ncbi Distant disease-free interval, site of first relapse and post-relapse survival in BRCA1- and BRCA2-associated compared to sporadic breast cancer patients
    Mieke Kriege
    Department of Medical Oncology, Rotterdam Family Cancer Clinic, Erasmus MC Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands
    Breast Cancer Res Treat 111:303-11. 2008
    Data on distant disease-free interval (DDFI) and the localization of the first distant metastasis (DM) in BRCA1- and BRCA2-associated breast cancer (BC) patients are as yet scarcely available.
  79. pmc Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients
    Eunjung Lee
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, USC Norris Comprehensive Cancer Center, Los Angeles, CA 90089 9175, USA
    Breast Cancer Res 10:R19. 2008
    ..to determine the significance of unclassified variants (UVs) in the breast cancer susceptibility genes BRCA1/BRCA2, but no study has systematically assessed whether women carrying the suspected deleterious UVs have ..
  80. doi BRCA1/BRCA2 mutation status and clinical-pathologic features of 108 male breast cancer cases from Tuscany: a population-based study in central Italy
    Laura Ottini
    Department of Experimental Medicine, University of Rome La Sapienza, 00161 Rome, Italy
    Breast Cancer Res Treat 116:577-86. 2009
    ..The strongest genetic risk factor for MBC is represented by inherited BRCA2 mutations, whereas the association between MBC and BRCA1 mutations is less clear...
  81. ncbi M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the dissociation of the BRCA2-P/CAF complex
    Horng Ru Lin
    Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245, USA
    J Biol Chem 278:35979-87. 2003
    b>BRCA2 is a breast tumor susceptibility gene encoding a 390-kDa protein with functions in maintaining genomic stability and cell cycle progression...
  82. doi The c.156_157insAlu BRCA2 rearrangement accounts for more than one-fourth of deleterious BRCA mutations in northern/central Portugal
    Ana Peixoto
    Department of Genetics, Portuguese Oncology Institute, Rua Dr Antonio Bernardino de Almeida, 4200 072, Porto, Portugal
    Breast Cancer Res Treat 114:31-8. 2009
    We evaluated the contribution of an Alu insertion in BRCA2 exon 3 (c.156_157insAlu) to inherited predisposition to breast/ovarian cancer in 208 families originated mostly from northern/central Portugal. We identified the c...
  83. ncbi Effect of BRCA mutations on the length of survival in epithelial ovarian tumors
    Y Ben David
    Department of Gynecology, Haemek Medical Center, Afula
    J Clin Oncol 20:463-6. 2002
    ..To study the role of BRCA mutations in ovarian cancer survival...
  84. doi The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage
    E M Bahassi
    Department of Cell and Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Oncogene 27:3977-85. 2008
    ....
  85. pmc Rad51 overexpression rescues radiation resistance in BRCA2-defective cancer cells
    Erika T Brown
    Department of Pathology, University of Colorado Health Sciences Center, RC 1 South Tower, 12801 East 17th Avenue, Aurora, Colorado 80010 7163, USA
    Mol Carcinog 48:105-9. 2009
    Breast cancers with BRCA2 mutations exhibit DNA repair defects and are particularly sensitive to radiation...
  86. doi Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age
    Dorina M Van Der Kolk
    Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Breast Cancer Res Treat 124:643-51. 2010
    ..1188 female mutation carriers and first-degree female relatives in 185 families with a pathogenic BRCA1 or BRCA2 mutation. The occurrence of breast cancer, contralateral breast cancer and ovarian cancer was recorded...
  87. pmc Germline BRCA mutations denote a clinicopathologic subset of prostate cancer
    David J Gallagher
    Clinical Genetics Service, Department of Medicine, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 16:2115-21. 2010
    ..Increased prostate cancer risk has been reported for BRCA mutation carriers, but BRCA-associated clinicopathologic features have not been clearly defined...
  88. doi Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer
    Shiyu Zhang
    Women s College Research Institute, University of Toronto, 790 Bay Street, 7th Floor, Toronto, ON, Canada M5G 1N8
    Gynecol Oncol 121:353-7. 2011
    ..Most inherited cases of ovarian cancer are due to a germline mutation in BRCA1 or BRCA2. It is important to have an accurate estimate of the proportion of ovarian cancer patients who carry a mutation ..
  89. doi Characterization of BRCA1 and BRCA2 splicing variants: a collaborative report by ENIGMA consortium members
    Mads Thomassen
    Department of Clinical Genetics, Odense University Hospital, Soenderboulevard 29, 5000 Odense C, Denmark
    Breast Cancer Res Treat 132:1009-23. 2012
    Mutations in BRCA1 and BRCA2 predispose carriers to early onset breast and ovarian cancer. A common problem in clinical genetic testing is interpretation of variants with unknown clinical significance...
  90. ncbi Greek BRCA1 and BRCA2 mutation spectrum: two BRCA1 mutations account for half the carriers found among high-risk breast/ovarian cancer patients
    Irene Konstantopoulou
    Molecular Diagnostics Laboratory, I R RP, National Center for Scientific Research Demokritos, Athens, Greece
    Breast Cancer Res Treat 107:431-41. 2008
    ..Our results indicated 16 and 5 breast/ovarian cancer families bearing deleterious mutations in the BRCA1 and BRCA2 genes, respectively. Two novel BRCA2 germline mutations (G4X and 3783del10) are reported here for the first time...
  91. pmc Structural basis for recruitment of BRCA2 by PALB2
    Antony W Oliver
    Cancer Research UK DNA Repair Enzymes Group, Section of Structural Biology, 237 Fulham Road, London SW3 6JB, UK
    EMBO Rep 10:990-6. 2009
    The breast cancer 2, early onset protein (BRCA2) is central to the repair of DNA damage by homologous recombination...
  92. pmc The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment
    P L Chen
    Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center, San Antonio, TX 78245, USA
    Proc Natl Acad Sci U S A 95:5287-92. 1998
    The BRCA2 gene was identified based on its involvement in familial breast cancer...
  93. ncbi Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada
    Harvey A Risch
    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, PO Box 208034, New Haven, CT 06520 8034, USA
    J Natl Cancer Inst 98:1694-706. 2006
    BRCA1 and BRCA2 mutations in general populations and in various types of cancers have not been well characterized...
  94. pmc Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
    Antonis C Antoniou
    Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, UK
    Am J Hum Genet 82:937-48. 2008
    Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families...
  95. doi The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain
    Roger L Milne
    Unidad de Genotipación CEGEN and Grupo de Genética Humana, Programa de Genética del Cáncer Humano, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
    Clin Cancer Res 14:2861-9. 2008
    It is not clear that the published estimates of the breast and ovarian cancer penetrances of mutations in BRCA1 and BRCA2 can be used in genetic counseling in countries such as Spain, where the incidence of breast cancer in the general ..
  96. pmc Variation of breast cancer risk among BRCA1/2 carriers
    Colin B Begg
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    JAMA 299:194-201. 2008
    The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers.
  97. ncbi One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations: results of a prospective study in Southern Sweden
    S Malander
    Department of Oncology, The Jubileum Institution, University Hospital, 221 85 Lund, Sweden
    Eur J Cancer 40:422-8. 2004
    ..We report here the results of a full mutational screening analysis for germ line BRCA1 and BRCA2 mutations in 161 patients with invasive epithelial ovarian carcinomas...
  98. ncbi Differences in the frequency and distribution of BRCA1 and BRCA2 mutations in breast/ovarian cancer cases from the Basque country with respect to the Spanish population: implications for genetic counselling
    E Beristain
    Laboratorio de Genetica Molecular, Hospital de Cruces, Pza de Cruces s n, 48903 Barakaldo, Bizkaia, Spain
    Breast Cancer Res Treat 106:255-62. 2007
    The prevalence of unique and recurrent BRCA1 and BRCA2 pathogenic mutations and unclassified variants varies among different populations...
  99. pmc Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions: implications for prediction of pathogenicity
    Logan C Walker
    Queensland Institute of Medical Research, Brisbane, Australia
    Hum Mutat 31:E1484-505. 2010
    ..approaches and in vitro assays are useful for the classification of exonic sequence variants in BRCA1 and BRCA2, but these currently rely on the assumption that changes in protein function are the major biological mechanism of ..
  100. ncbi Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13
    R Wooster
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, UK
    Science 265:2088-90. 1994
    ..This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13...
  101. ncbi EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer
    Luke Hughes-Davies
    Cancer Research UK Wellcome Trust Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
    Cell 115:523-35. 2003
    The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer...

Research Grants76

  1. Obesity susceptibility loci and breast cancer risk in BRCA1 and BRCA2 mutation ca
    JONATHAN ANDREW MITCHELL; Fiscal Year: 2013
    ..lead involves investigating if genetic predisposition to obesity modifies breast cancer risk in female BRCA1 and BRCA2 mutation carriers...
  2. Wei Zheng; Fiscal Year: 2015
    ..genetic factors, along with high-penetrance susceptibility genes reported previously (such as the BRCA1 and BRCA2 genes), explain only a small fraction of genetic variation for breast cancer...
  3. ERICA LYNN CAIN; Fiscal Year: 2014
    ..of drug resistance in a cancer population is resistance to Poly ADP-Ribose Polymerase (PARP) inhibitors (PARPi) in BRCA2-deficient cancers. Both Breast Cancer 2 susceptibility protein (BRCA2) and PARP1 function in DNA repair...
  4. Simon N Powell; Fiscal Year: 2016
    ..by applicant): The DNA damage response and DNA repair defects found in cells with a deficiency of the BRCA1 or BRCA2 protein have been extensively characterized in the last decade...
  5. PHENOTYPIC RISK MARKERS IN BRCA1 MUTATION CARRIERS
    Gail Tomlinson; Fiscal Year: 2002
    The identification of the two major breast cancer predisposition genes, BRCA1 and BRCA2, has heralded an era of genetic risk assessment which in turn has helped to facilitate the development of new strategies for early detection and ..
  6. Mechanisms of Carcinogenesis in BRCA2 Mutant Cells
    Jeffrey Holt; Fiscal Year: 2005
    ..is mostly cytoplasmic in brca2--, and that wildtype BRCA2 expression relocates Rad51 to the nucleus whereas mutant BRCA2 expression does not effect Rad51 localization. These fundings lead to the following hypotheses: 1...
  7. ROLES OF BRCA1 AND BRCA2 IN BREAST CARCINOGENESIS
    Daniel Silver; Fiscal Year: 2003
    The recently isolated tumor suppressor genes, BRCA1 and BRCA2, appear to play key roles in preventing breast and ovarian carcinoma...
  8. Mechanistic Studies of BRCA2-RAD51 Mediated DNA Repair
    Erika Brown; Fiscal Year: 2006
    ..Her studies have shown that the DNA repair protein RAD51, which associates with the protein BRCA2, fails to move from the cytoplasm into the nucleus after induction of double-strand DNA breaks in BRCA2-defective ..
  9. Early Detection of Pancreatic Cancer Using Ice COLD-PCR
    Grant Wu; Fiscal Year: 2012
    ..that lead to Her-2 overexpression and p16 inactivation;(3) in Stage 3, mutations occur in the TP53, DPC4, and BRCA2 genes...
  10. Rahul Nene; Fiscal Year: 2015
    ..The success of poly(ADP-ribose) polymerase (PARP) inhibitors against cancers with defects in the BRCA1 and BRCA2 genes demonstrates that a synthetic lethality inspired approach can be successful in the context of defects in ..
  11. Adherence to Cancer Risk Management Among Unaffected BRCA1/2Mutation Carriers
    Adam H Buchanan; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Inherited mutations in the BRCA1 and BRCA2 genes lead to significantly increased cancer risks (up to 66% and 46% for lifetime breast and ovarian cancer risks, respectively)...
  12. FERGUS JOSEPH COUCH; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Women with germline inactivating mutations in the BRCA1 and BRCA2 genes are at significantly elevated risk of breast and ovarian cancer...
  13. Bing Xia; Fiscal Year: 2016
    Heterozygous germline mutations in BRCA2 predispose female carriers to breast cancer and also lead to increased risks of ovarian, male breast, prostate, and pancreatic cancers...
  14. LOH at BRCA1/BRCA2 Loci in Mutation Carriers as a Precursor to Breast Tumorigenes
    Mark A Brenneman; Fiscal Year: 2010
    Women who carry mutations in the BRCA1 or BRCA2 tumor suppressor genes are at extreme risk for breast cancer. BRCA1 or BRCA2 mutation carriers are heterozygous, but their breast tumors typically show loss of heterozygosity (LOH), i.e...
  15. BRCA1 and Familial Pancreatic Cancer
    Alison Klein; Fiscal Year: 2007
    ..Inherited mutations in the BRCA2 gene account for 1 in 6 cases of familial pancreatic cancer cases and 1 in 14 cases of apparently sporadic ..
  16. Identifying Ovarian Cancer Susceptibility Alleles using Genome-Wide Scan Data
    Celeste Leigh Pearce; Fiscal Year: 2012
    ..Family history is a strong risk factor for ovarian cancer;mutations in BRCA1 and BRCA2 cause ovarian cancer, but account for only ~40% of the excess familial risk of the disease, strongly suggesting ..
  17. Validation of an Antibody Test for Early Diagnosis of Ovarian Cancer
    Michael A Tainsky; Fiscal Year: 2013
    ..This results in about 14,000 deaths per year in the US. About 1 in 200 women in North America carries BRCA1 or BRCA2 mutations and 5 million women with a family history of ovarian cancer in a first or second degree relative...
  18. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2015
    ..The high-risk breast cancer susceptibility genes BRCA1, BRCA2, PTEN, and TP53 were all discovered more than a decade ago...
  19. Racial Differences in BRCA1/2 Testing: Patients or Providers?
    Peter W Groeneveld; Fiscal Year: 2013
    ..Testing for mutations in the breast cancer susceptibility genes, BRCA1and BRCA2, is one of the earliest examples of cancer genetic susceptibility testing to become incorporated into clinical ..
  20. Analyses of AD relevant phenotypes in neural cells derived from human iPSCs
    Tracy L Young-Pearse; Fiscal Year: 2012
    ..investigate the mechanistic consequences of both a strong, dominantly inherited familial Alzheimer's disease (fAD) mutation and an allelic variant in APOE that increases risk for AD...
  21. Eric C Greene; Fiscal Year: 2015
    ..In addition, defects in BRCA2 account for at least 5% of all breast cancers and also confer a genetic predisposition to ovarian cancer...
  22. A novel model system for risk assessment of BRCA carriers
    RORY LANDON COCHRAN; Fiscal Year: 2013
    ..It is believed that the breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2, account for the majority of germ-line mutations in families with a genetic predisposition for developing breast ..
  23. Genetics of Breast Cancer in Blacks
    Olufunmilayo Olopade; Fiscal Year: 2006
    ..With the cloning of BRCA1 and BRCA2 genes, there is an urgent need to identify mutations among different ethnic populations in order to study mutation ..
  24. Pharmacogenomics of Human P450 Oxidoreductase
    Walter L Miller; Fiscal Year: 2012
    ..POR is a 680 amino-acid, 78 kDa protein that contains two flavins, a flavin adenine dinucleotide moiety (FAD), and a flavin mononucleotide (FMN). There is substantial genetic variation in the hepatic P450 enzymes...
  25. Non-invasive Assessment of Tissue Engineered Human Oral Mucosa
    Mary Ann Mycek; Fiscal Year: 2012
    ..of the cellular component of the EVPOME via the redox state of endogenous fluorophores flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH)...
  26. MEHNAAZ FATIMA ALI; Fiscal Year: 2015
    ..The redox properties of GOx are dependent on the presence of its co-factor flavin adenine dinucleotide (FAD). The removal of FAD reversibly renders the enzyme inactive without permanently denaturing the enzyme structure...
  27. Todd C Holmes; Fiscal Year: 2016
    ..sensitivity is mediated through light-activated changes in the redox state of the flavin adenine dinucleotide (FAD) chromophore bound to dCry which then couples to a redox sensor in cytoplasmic potassium channel subunits and ..
  28. Raymond J Kelleher; Fiscal Year: 2016
    ..in presenilin 1 (PS1) and presenilin 2 (PS2) account for ~90% of all identified causative mutations in familial AD (FAD), highlighting the importance of presenilins (PS) in AD pathogenesis...
  29. Mary Beth Terry; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): The discovery of BRCA1 and BRCA2 has resulted in more appropriate targeting of preventive and screening strategies for breast cancer...
  30. Neil W Kowall; Fiscal Year: 2014
    ..potential substrates for LSD1, a key enzyme regulating protein methylation that shares considerable homology with FAD-dependent polyamine oxidases...
  31. BRCA2 Hereditary Ovarian Cancer Tissue Truncation Test
    Jeffrey T Holt; Fiscal Year: 2010
    ..II proposal, 2R42CA124191-02, which received a priority score of 181, to develop a tissue-based genetic test for BRCA2 hereditary ovarian cancer...
  32. Development of a BRCA Breast Cancer Diagnostic Test
    Jeffrey Holt; Fiscal Year: 2007
    ..This proposal aims to develop a tissue-based genetic test for BRCA2 hereditary breast cancer using a tissue-based IHC method...
  33. BRCA2 Hereditary Ovarian Cancer Tissue Truncation Test
    Jeffrey Holt; Fiscal Year: 2007
    ..revision of a Phase I STTR proposal that received a score of 177, to develop a tissue-based genetic test for BRCA2 hereditary ovarian cancer...
  34. Elizabeth R Jacobs; Fiscal Year: 2016
    ..metabolic coenzymes Nicotinamide Adenine Dinucleotide (reduced form is NADH) and Flavine Adenine Dinucleotide (FAD) are the primary electron carriers in oxidative phosphorylation...
  35. Mitoenergetic Failure in Brain Aging
    Gregory J Brewer; Fiscal Year: 2013
    ..higher levels of ROS with lower glutathione antioxidant and maintain a more oxidized redox potential [ NAD(P)H / FAD ], all of which contribute to increased susceptibility to toxic stressors such as glutamate and beta-amyloid...
  36. Edward H Egelman; Fiscal Year: 2016
    ..greatly elevated by the understanding that proteins such as the product of the breast cancer susceptibility gene BRCA2 interact with Rad51 and target Rad51 to sites of DNA damage...
  37. Towards a Model of Fanconi Anemia
    BEVERLY JO TOROK STORB; Fiscal Year: 2010
    ..We plan to optimize the methods for culture, genetic manipulation, and transplantation of SSC in dogs, and to use this technology to set the stage for producing a canine model of Fanconi Anemia. ..
  38. The Roles of Trm9 and tRNA Methylation in the DNA Damage Response
    Thomas J Begley; Fiscal Year: 2010
    ..Excitingly, we have linked human Trm9 activity to the regulation of specific DNA repair proteins (Rad54, Brca2, Bccip, Ercc8, Tdg, Msh4, Rad51, and DNA Ligase IV), and we will study how Trm9 affects their damage-induced ..
  39. Suman Jayadev; Fiscal Year: 2016
    ..2 (PSEN2) deficiency is associated with an exaggerated pro-inflammatory response in microglia and that the fAD associated PSEN2 N141I mutation leads to decreased gamma- secretase activity in microglia...
  40. Comparative effectiveness of Brain Imaging and Blood Biomarkers in Alzheimer??s d
    Orly Lazarov; Fiscal Year: 2010
    ..Our studies in mouse models of Familial Alzheimer's disease (FAD) revealed that neurogenesis is severely compromised in these mice...
  41. ANIL KUMAR JAISWAL; Fiscal Year: 2016
    ..About 5-10% is the familial cases, which are attributed to deleterious mutations in BRCA1 and BRCA2. The majority of the remaining breast cancer cases are also suspected to contain genetic component that affects ..
  42. Zeiss 2-photon (2P) LSM780 laser scanning confocal microscope
    Moshe Levi; Fiscal Year: 2013
    ..Dynamic imaging of metabolism is achieved in part through monitoring changes in NAD(P)H and FAD lifetimes...
  43. Cations and ROS in Modulating Mitochondrial Function in Normal and Ischemic Heart
    Ranjan K Dash; Fiscal Year: 2013
    ..bioenergetics and electrophysiology (changes in trans-matrix cation concentrations and fluxes, NADH and FAD redox states, membrane potential, respiration, and ROS production with normal and abnormal perturbations in extra-..
  44. Carola Anke Neumann; Fiscal Year: 2014
    ..sequence into mammary epithelial cells isolated from Prdx1-/-MMTV-ErbB-2 mice and transplant cells into clear fad pads of NCR nude mice, to observe if nuclear Prdx1 decreases incidence of breast cancer or tumor burden...
  45. James R Bamburg; Fiscal Year: 2014
    ..rods that initiate and exacerbate synaptic dysfunction typical of both sporadic (SAD) and familial AD (FAD)...
  46. Environmental exposure: Susceptibility alleles in a DNA damage response pathway
    Peter J Stambrook; Fiscal Year: 2013
    ..strand DNA break involves ATM and other DNA damage response proteins including CHEK2, Cdc25A, Plk3, BRCA1 and BRCA2. Several genes in this pathway, which contribute to genomic stability, have variant alleles that predispose to ..
  47. Suman Jayadev; Fiscal Year: 2015
    ..Familial Alzheimer disease (fAD) is associated with mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PS1) and ..
  48. Tina M Iverson; Fiscal Year: 2016
    ..These include a covalently-bound FAD cofactor, three distinct iron- sulfur clusters, a membrane-bound quinone, and a b heme cofactor...
  49. Re-expression of Aberrantly Silenced Genes Induced by Polyamine Analogues
    Robert A Casero; Fiscal Year: 2013
    ..The first histone lysine demethylase discovered, LSD1, an FAD-dependent oxidase, targets mono- and dimethyl-lysine 4 histone 3 (H3K4me1 &H3K4me2)...
  50. The Molecular Physiology of Renalase
    Gary V Desir; Fiscal Year: 2010
    ..That effort led to the discovery of renalase, a novel FAD-dependent amine oxidase that is expressed in kidney, and heart...
  51. An iPS Disease-in-a-Dish Model of Familial Alzheimers
    Terrence Town; Fiscal Year: 2012
    ..In this regard, transgenic mice harboring mutations in one or more genes that cause early-onset familial AD (fAD) have been enormously helpful, both in terms of interrogating potential therapeutic targets and also for ..
  52. Hong Yan; Fiscal Year: 2015
    ..Mutations in many DSB repair genes, such as Werner syndrome gene and Bloom syndrome gene, BRCA1, and BRCA2, dramatically increase the risk of cancer...
  53. Structural/Functional Modularity in Nitric Oxide Synthase
    Linda J Roman; Fiscal Year: 2012
    ..are that the molecular design of the NOS isoforms, while requiring the same cofactors and prosthetic groups (FAD, FMN, Fe-protoporphyrin IX, Zn and tetrahydrobiopterin), is adapted in each isoform to satisfy its specific ..
  54. Susan M Wolf; Fiscal Year: 2015
    ..germline carriers of mutations in genes known to confer increased risk of diseases other than pancreatic cancer: BRCA2 (breast &ovarian cancer), CDKN2A/p16 (malignant melanoma), and CFTR (cystic fibrosis in offspring)...
  55. Penn Center for ELSI Research in Emerging Genetic Technologies in Health Care
    Reed E Pyeritz; Fiscal Year: 2012
    ..To follow a cohort of African-American (and other minority) women who have been counseled for testing of BRCA1 and BRCA2 to assess the longer-term psychological, social, and medical impact of risk counseling and genetic testing on ..
  56. Impact of Presenilin 2 Mutation and Deficiency on Microglial Function
    Suman Jayadev; Fiscal Year: 2010
    ..neurodegenerative disease by characterizing the phenotype of microglia deficient in PS2 or expressing Familial AD (FAD) PS2 mutations in vitro...
  57. FASEB SRC on Genetic Recombination and Genome Rearrangements
    JOHN HJ PETRINI; Fiscal Year: 2011
    ..Furthermore, the product of the BRCA2 gene, which is mutated in a subset of hereditary breast cancers, interacts directly with Rad51 and is essential ..
  58. TGF-beta polymorphisms and breast cancer in families
    Boris Pasche; Fiscal Year: 2013
    ..Validated SNPs will be further examined by the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. To search for the causal variant(s) we will 1) re-sequence the validated region(s) in 200 patients that carry the ..
  59. Nikolaos K Robakis; Fiscal Year: 2016
    ..Reduction in brain glucose metabolism is also observed in familial AD (FAD) patients and may occur years before disease onset in carriers of presenilin-1 (PS1) FAD mutations implicating PS1 ..
  60. Colin Thorpe; Fiscal Year: 2016
    ..This application deals with several evolutionarily-related FAD-dependent sulfhydryl oxidases: members of the Quiescin-sulfhydryl oxidase (QSOX) family of flavoproteins, and a ..
  61. Predicting pancreatic cancer responses for a Parp inhibitor-based clinical trial
    Michael G Goggins; Fiscal Year: 2010
    ..majority of genes mutated in patients with familial pancreatic cancer are in the homologous DNA repair including BRCA2/BRCA1/PALB2/Fanconi Anemia pathway mutations...
  62. Presenilins and Cell Adhesion Molecules
    Angele Parent; Fiscal Year: 2012
    ..Interestingly, using PS1 M146V knock-in mice we find that expression of FAD-linked mutant also elevates cAMP-dependent signaling in cultured neurons, and leads to increased spine density in ..
  63. KENNETH TERCYAK; Fiscal Year: 2014
    ..Over 100,000 women have been tested for mutations in the 2 major breast cancer risk-conferring genes BRCA1 and BRCA2 (BRCA1/2), making life- altering decisions based upon this information...
  64. Targeting invasion and DNA DSB repair in glioma with a multi-pronged approach.
    KRISTOFFER CARL VALERIE; Fiscal Year: 2012
    ..AZD2281 targets and kills tumor cells with mutations in BRCA1/BRCA2, or cells that are defective in homologous recombination repair (HRR) failing to repair DNA double-strand breaks (..
  65. Regulation of APP Pathway Gene Promoters in Alzheimer's
    Debomoy K Lahiri; Fiscal Year: 2011
    ..Cell lines from families with characterized FAD will be analyzed for differential expression of the APP and BACE genes...
  66. NIALL GEORGE HOWLETT; Fiscal Year: 2015
    ..The FA proteins function cooperatively with the tumor suppressor proteins BRCA1 and BRCA2 (FANCD1) in the FA- BRCA pathway to repair damaged DNA and to prevent cellular transformation...
  67. Development of a HTS assay for modulators of presenilin 1 conformation
    Oksana Berezovska; Fiscal Year: 2010
    ..over 150 known mutations in PS1, scattered throughout the molecule, all lead to autosomal dominant familial AD (FAD) and enhance A[unreadable] 42 generation...
  68. Peter M Glazer; Fiscal Year: 2016
    ..Importantly, the 3E10 monoclonal antibody, by itself, is synthetically lethal to BRCA2-deficient cancer cells, but is otherwise non-toxic to DNA repair- proficient cells in culture or to mice in vivo...
  69. ILYA B BEZPROZVANNY; Fiscal Year: 2016
    ..Missense mutations in presenilins account for 40% of familial AD (FAD) cases...
  70. Central and endocrine stress pathway contributions to Alzheimers Disease
    Nicholas J Justice; Fiscal Year: 2013
    ..First, I plan to characterize aging mice carrying Familial Alzheimer's Disease (FAD) mutations that acquire AD pathologies, for changes in anxiety related behavior, HPA axis function, and molecular ..
  71. Characterization of an FAD pathogenic PS1 mutation with complete loss of activity
    HANNAH LOUISE BRAUTIGAM; Fiscal Year: 2013
    ..Rare, autosomal dominant familial forms of AD (FAD) have provided us with most of what is currently known of the molecular basis of the disease...
  72. FASEB SRC: Genetic Recombination and Genome Rearrangements
    Wolf Dietrich Heyer; Fiscal Year: 2013
    ..Several timely issues will be discussed, including the role of the breast cancer susceptibility gene BRCA2 in the control of recombination and the role of recombination in repair of DNA damage caused by cancer treatment ..
  73. Susan J Ramus; Fiscal Year: 2016
    ..Germline mutations in the high- penetrance susceptibility genes BRCA1 and BRCA2 confer EOC risks of around 50% by age 70...
  74. Peripheral Biomarkers in Familial Alzheimer's Disease
    Paul Coleman; Fiscal Year: 2009
    ..In this proposal we focus largely on the mutated gene for PS1 since it is a frequently mutated gene among the FAD gene mutations...
  75. FAA AND FAD GENES AND PROTEINS
    Manuel Buchwald; Fiscal Year: 1999
    ..and confirmed its identity by the identification of mutations in FA-A cells; he also has a strong candidate for the FAD gene...
  76. STRUCTURAL DETERMINANTS OF FAD and FMN-REQUIRING ENZYMES
    Bettie Sue Masters; Fiscal Year: 2005
    This proposal emanates from the interests of the Principal Investigator in flavoproteins containing both FAD and FMN as prosthetic groups, extending from her early studies on NADPI-I-cytochrome P450 reductase (CYPOR) to the three nitric ..