germ line mutation


Summary: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.

Top Publications

  1. ncbi A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1
    Y Miki
    Department of Medical Informatics, University of Utah Medical Center, Salt Lake City 84132
    Science 266:66-71. 1994
  2. ncbi Hereditary colorectal cancer
    Henry T Lynch
    Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebr 68178, USA
    N Engl J Med 348:919-32. 2003
  3. ncbi Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer
    Ian P M Tomlinson
    Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44, Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Genet 30:406-10. 2002
  4. ncbi Germ-line mutations in nonsyndromic pheochromocytoma
    Hartmut P H Neumann
    Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany
    N Engl J Med 346:1459-66. 2002
  5. ncbi The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1
    Delmar Muniz Lourenço
    Unidade de Endocrinologia Genética, LIM 25, Endocrinlologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
    Clinics (Sao Paulo) 62:465-76. 2007
  6. ncbi A serine/threonine kinase gene defective in Peutz-Jeghers syndrome
    A Hemminki
    Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland
    Nature 391:184-7. 1998
  7. 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
  8. ncbi Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers
    G L Mutter
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Natl Cancer Inst 92:924-30. 2000
  9. ncbi Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer)
    Heather Hampel
    Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, Columbus, USA
    N Engl J Med 352:1851-60. 2005
  10. ncbi Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations
    Hartmut P H Neumann
    Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany
    JAMA 292:943-51. 2004

Detail Information

Publications345 found, 100 shown here

  1. ncbi A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1
    Y Miki
    Department of Medical Informatics, University of Utah Medical Center, Salt Lake City 84132
    Science 266:66-71. 1994
    ..Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology...
  2. ncbi Hereditary colorectal cancer
    Henry T Lynch
    Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebr 68178, USA
    N Engl J Med 348:919-32. 2003
  3. ncbi Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer
    Ian P M Tomlinson
    Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44, Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Genet 30:406-10. 2002
    ..Our results provide clues to the pathogenesis of fibroids and emphasize the importance of mutations of housekeeping and mitochondrial proteins in the pathogenesis of common types of tumor...
  4. ncbi Germ-line mutations in nonsyndromic pheochromocytoma
    Hartmut P H Neumann
    Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany
    N Engl J Med 346:1459-66. 2002
  5. ncbi The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1
    Delmar Muniz Lourenço
    Unidade de Endocrinologia Genética, LIM 25, Endocrinlologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
    Clinics (Sao Paulo) 62:465-76. 2007
  6. ncbi A serine/threonine kinase gene defective in Peutz-Jeghers syndrome
    A Hemminki
    Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland
    Nature 391:184-7. 1998
    ..Peutz-Jeghers syndrome is therefore the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase...
  7. 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
    ..Each mutation causes serious disruption to the open reading frame of the transcriptional unit. The results indicate that this is the BRCA2 gene...
  8. ncbi Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers
    G L Mutter
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Natl Cancer Inst 92:924-30. 2000
    ..Testing the hypothesis that altered PTEN function precedes the appearance of endometrial adenocarcinoma has been difficult, however, partly because of uncertainties in precancer diagnosis...
  9. ncbi Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer)
    Heather Hampel
    Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, Columbus, USA
    N Engl J Med 352:1851-60. 2005
    ..We assessed the frequency of such mutations in patients with colorectal cancer and examined strategies for molecular screening to identify patients with the syndrome...
  10. ncbi Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations
    Hartmut P H Neumann
    Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany
    JAMA 292:943-51. 2004
    ..In both syndromes, pheochromocytomas as well as head and neck paragangliomas occur; however, details for individual risks and other clinical characteristics are unknown...
  11. pmc P53 germline mutations in childhood cancers and cancer risk for carrier individuals
    A Chompret
    , Institute Gustave Roussy, Villejuif, France
    Br J Cancer 82:1932-7. 2000
    ..The risk of cancer associated with such mutations is very high and no evidence of low penetrance mutation was found. These mutations are frequently inherited but de novo mutations are not rare...
  12. ncbi Mutations of the human PTEN gene
    D Bonneau
    Department of Medical Genetics, University of Poitiers, Poitiers, France
    Hum Mutat 16:109-22. 2000
    ..A mutagenesis by insertion-deletion in repetitive elements is however specifically observed in endometrial carcinomas...
  13. ncbi Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH
    Oliver M Sieber
    Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom
    N Engl J Med 348:791-9. 2003
    ..Tumors from affected persons displayed excess somatic transversions of a guanine-cytosine pair to a thymine-adenine pair (G:C-->T:A) in the APC gene...
  14. ncbi Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome
    D Liaw
    Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Nat Genet 16:64-7. 1997
    ..Thus, PTEN appears to behave as a tumour suppressor gene in the germline. Our data also imply that PTEN may play a role in organizing the relationship of different cell types within an organ during development...
  15. ncbi High frequency of HIF-1alpha overexpression in BRCA1 related breast cancer
    Petra van der Groep
    Department of Pathology, University Medical Center, 3508 GA, Utrecht, The Netherlands
    Breast Cancer Res Treat 111:475-80. 2008
    ..This points to an important role of hypoxia and its key regulator HIF-1alpha in hereditary breast carcinogenesis...
  16. ncbi Pituitary adenoma predisposition caused by germline mutations in the AIP gene
    Outi Vierimaa
    Department of Clinical Genetics, Oulu University Hospital, 90029 Oulu, Finland
    Science 312:1228-30. 2006
    ..Typically, PAP patients do not display a strong family history of pituitary adenoma; thus, AIP is an example of a low-penetrance tumor susceptibility gene...
  17. ncbi Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome
    S B Gruber
    Division of Molecular Medicine and Genetics, University of Michigan, Ann Arbor 48109, USA
    Cancer Res 58:5267-70. 1998
    ..Additional somatic mutational events underlie the progression of hamartomas to adenocarcinomas, and some of these somatic mutations are common to the later stages of tumor progression seen in the majority of colorectal carcinomas...
  18. ncbi Association between nonrandom X-chromosome inactivation and BRCA1 mutation in germline DNA of patients with ovarian cancer
    R E Buller
    Department of Pharmacology, The University of Iowa Hospitals and Clinics, Iowa City 52242 1009, USA
    J Natl Cancer Inst 91:339-46. 1999
    ..This scenario could represent a previously unrecognized mechanism for development of hereditary cancers. We investigated whether such a mechanism might contribute to the development of hereditary ovarian cancers...
  19. pmc Mutations in CHEK2 associated with prostate cancer risk
    Xiangyang Dong
    Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic Mayo Medical School, Rochester, MN 55905, USA
    Am J Hum Genet 72:270-80. 2003
    ..Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer...
  20. ncbi Heterogeneous mutation processes in human microsatellite DNA sequences
    H Ellegren
    Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyvagen 18D, SE 752 36 Uppsala, Sweden
    Nat Genet 24:400-2. 2000
    ..An excess of paternally transmitted mutations (male-to-female ratio of 4.9) supports a male-biased mutation rate in the human genome...
  21. ncbi Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations
    A M Goldstein
    Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892 7236, USA
    J Natl Cancer Inst 92:1006-10. 2000
    ..CDKN2A is a tumor suppressor gene that encodes p16 (which inhibits activity of the cyclin D1-CDK4 complex) with germline mutations detected in 10%-25% of melanoma-prone families, some of whom are also prone to pancreatic cancer...
  22. ncbi Desmoglein 2 is expressed abnormally rather than mutated in familial and sporadic gastric cancer
    Karin Biedermann
    Institute of Pathology, Klinikum rechts der Isar, Technische Universitat Munchen, Germany
    J Pathol 207:199-206. 2005
    ..Somatic mutations in the gene do not seem to be a very frequent inactivation event and the finding of no clear pathogenic germline mutation rules out Dsg2 as a major gastric cancer predisposition gene...
  23. ncbi Arg462Gln sequence variation in the prostate-cancer-susceptibility gene RNASEL and age of onset of hereditary non-polyposis colorectal cancer: a case-control study
    Stefan Kruger
    Department of Surgical Research, Dresden University of Technology, Dresden, Germany
    Lancet Oncol 6:566-72. 2005
  24. pmc Mutation cluster region, association between germline and somatic mutations and genotype-phenotype correlation in upper gastrointestinal familial adenomatous polyposis
    Christopher Groves
    Academic Unit and Polyposis Registry, Saint Mark s Hospital, Harrow, United Kingdom
    Am J Pathol 160:2055-61. 2002
    ..Compared with colonic tumors, however, retention of a greater number of beta-catenin binding/degradation repeats is optimal for tumorigenesis in upper gastrointestinal FAP...
  25. ncbi Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma
    O Gimm
    Department of Internal Medicine, The Ohio State University, Columbus 43210, USA
    Cancer Res 60:6822-5. 2000
  26. ncbi Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer
    Virginia Piñol
    Department of Gastroenterology, Institut de Malalties Digestives, Hospital Clinic, University of Barcelona, Barcelona, Spain
    JAMA 293:1986-94. 2005
    ..Recently, the National Cancer Institute outlined a new set of recommendations, the revised Bethesda guidelines, for the identification of individuals with HNPCC who should be tested for microsatellite instability...
  27. ncbi Germline p16 mutations in familial melanoma
    C J Hussussian
    Laboratory of Genetic Disease Research, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892
    Nat Genet 8:15-21. 1994
    ..Functional analyses of these mutations will confirm those causally related to the development of familial melanoma...
  28. ncbi The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives
    A Yong Cao
    Breast Cancer Institute, Cancer Hospital Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, People s Republic of China
    Breast Cancer Res Treat 114:457-62. 2009
    ..Our results suggested that a detection of exon 4 before the assay of the whole PALB2 gene might be a cost-effective approach to the screening of Chinese population...
  29. ncbi Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance
    Yvonne M C Hendriks
    Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Gastroenterology 127:17-25. 2004
    ..Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers...
  30. pmc An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma
    R C Ribeiro
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 98:9330-5. 2001
    ..Therefore, this inherited R337H p53 mutation represents a low-penetrance p53 allele that contributes in a tissue-specific manner to the development of pediatric ACC...
  31. ncbi Ten genes for inherited breast cancer
    Tom Walsh
    Department of Medicine, University of Washington, Seattle, Washington 98195, USA
    Cancer Cell 11:103-5. 2007
    ..In addition, biallelic mutations in BRCA2, BRIP1, and PALB2 cause Fanconi anemia. The convergence of these genes in a shared role reveals underlying biology of these illnesses and suggests still other breast cancer genes...
  32. ncbi Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas
    Anne Paule Gimenez-Roqueplo
    AP HP, Hopital Europeen Georges Pompidou, Département de Génétique Moléculaire, Paris
    Cancer Res 63:5615-21. 2003
    ..These data strongly suggest that SDHB gene is a tumor suppressor gene and that the identification of germ-line mutations in SDHB gene in patients with ASPs should be considered as a high-risk factor for malignancy or recurrence...
  33. ncbi Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma
    Rodrigo A Toledo
    Unidade de Endocrinologia Genética, Faculdade de Medicina, Universidade de Sao Paulo, Av Dr Arnaldo 455 5 andar, Sao Paulo SP, Brazil 01246 903
    J Clin Endocrinol Metab 92:1934-7. 2007
    ..Recently mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were associated with familial pituitary adenoma predisposition...
  34. pmc Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk
    Shih Jen Hwang
    Section of Clinical Cancer Genetics, Department of Molecular Genetics, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Am J Hum Genet 72:975-83. 2003
    ..These results quantitatively illustrated the spectrum of cancer risk in germline p53 mutation carriers and will provide valuable reference for the evaluation and treatment of patients with cancer...
  35. ncbi Difference between evolutionarily effective and germ line mutation rate due to stochastically varying haplogroup size
    Lev A Zhivotovsky
    N I Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
    Mol Biol Evol 23:2268-70. 2006
  36. ncbi Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity
    I U Ali
    I U Ali, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892 7332, USA
    J Natl Cancer Inst 91:1922-32. 1999
    ..Further understanding of PTEN/MMAC1 gene mutations in different tumors and the physiologic consequences of these mutations is likely to open up new therapeutic opportunities for targeting this critical gene...
  37. ncbi Genetic testing in pheochromocytoma or functional paraganglioma
    Laurence Amar
    Universite Paris Descartes, Faculte de Medecine, France
    J Clin Oncol 23:8812-8. 2005
    ..To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl)...
  38. ncbi Early malignant progression of hereditary medullary thyroid cancer
    Andreas Machens
    Klinik fUr Allgemein, Viszeral, und Gefässchirurgie, Martin Luther Universitat Halle Wittenberg, Halle, Saale, Germany
    N Engl J Med 349:1517-25. 2003
  39. ncbi Germline mutations in PTEN are present in Bannayan-Zonana syndrome
    D J Marsh
    Nat Genet 16:333-4. 1997
  40. ncbi Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database
    Audrey Petitjean
    Group of Molecular Carcinogenesis and Biomarkers, International Agency for Research on Cancer IARC, World Health Organization, Lyon, France
    Hum Mutat 28:622-9. 2007
    ..These results provide new insights into the factors that shape mutation patterns and influence mutation phenotype, which may have clinical interest...
  41. ncbi Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex
    L S Kirschner
    Unit on Genetics and Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, USA
    Nat Genet 26:89-92. 2000
    ..We conclude that germline mutations in PRKAR1A, an apparent tumour-suppressor gene, are responsible for the CNC phenotype in a subset of patients with this disease...
  42. pmc Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer
    Valgerdur Birgisdottir
    The Icelandic Cancer Society, Molecular and Cell Biology Research Laboratory, Reykjavik, Iceland
    Breast Cancer Res 8:R38. 2006
    ..We examined the frequency of BRCA1 methylation in 143 primary sporadic breast tumours along with BRCA1 copy number alterations and tumour phenotype...
  43. ncbi The genetics of breast cancer susceptibility
    N Rahman
    Section of Cancer Genetics, Haddow Laboratories, Sutton, Surrey, United Kingdom
    Annu Rev Genet 32:95-121. 1998
    ..Finally, it is probable that the genes underlying a substantial component of susceptibility to breast cancer remain to be identified...
  44. ncbi UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan
    Leslie E Carlini
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    Clin Cancer Res 11:1226-36. 2005
  45. ncbi Polymorphisms G691S/S904S of RET as genetic modifiers of MEN 2A
    Mercedes Robledo
    Centro Nacional de Epidemiologia, Instituto de Salud Carlos III Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
    Cancer Res 63:1814-7. 2003
    ..36), suggesting that these polymorphisms may play a role as a low penetrance risk factor...
  46. ncbi Familial endometrial cancer in female carriers of MSH6 germline mutations
    J Wijnen
    Nat Genet 23:142-4. 1999
  47. ncbi Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer
    G R Bignell
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Cancer Res 58:1384-6. 1998
    ..The results indicate that mutations in LKB1 do not play an important role in the development of sporadic breast cancer...
  48. ncbi Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations
    Sian Jones
    Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK
    Hum Mol Genet 11:2961-7. 2002
    ..These findings confirm the role of MYH in colorectal adenoma and carcinoma predisposition...
  49. pmc Germline E-cadherin mutations in familial lobular breast cancer
    S Masciari
    J Med Genet 44:726-31. 2007
    ..This study aimed to investigate the frequency of germline CDH1 mutations in patients with LBC with early onset disease or family histories of breast cancer without DGC...
  50. pmc Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families
    N D Kauff
    J Med Genet 39:611-4. 2002
  51. ncbi Germline mutations of TP53 and BRCA2 genes in breast cancer/sarcoma families
    Siranoush Manoukian
    Medical Genetics Service, Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Milan, Italy
    Eur J Cancer 43:601-6. 2007
    ..These findings suggest that the screening of BRCA2, in addition to TP53, may be appropriate for the molecular characterisation of breast cancer/sarcoma families, with practical implications for counselling and clinical management...
  52. ncbi CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population
    Dace Pjanova
    Latvian Biomedical Research and Study Centre, Riga, Latvia
    Melanoma Res 17:185-91. 2007
    ..The detected CDK4 exon 2 mutation was found in only the seventh family identified worldwide with a germline CDK4 mutation...
  53. ncbi Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations
    D G Huntsman
    Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver, Canada
    N Engl J Med 344:1904-9. 2001
    ..We describe genetic screening, surgical management, and pathological findings in young persons with truncating mutations in CDH1 from two unrelated families with hereditary diffuse gastric cancer...
  54. ncbi RNASEL germline variants are associated with pancreatic cancer
    Detlef K Bartsch
    Department of Surgery, Philipps University, Marburg, Germany
    Int J Cancer 117:718-22. 2005
    ..04) than patients with the wild-type genotype. Our results suggest that RNASEL variants Glu265X and Arg462Gln may contribute to the tumorigenesis of sporadic and familial pancreatic cancer, which has to be proven in large scale studies...
  55. ncbi The ABC of APC
    N S Fearnhead
    Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK
    Hum Mol Genet 10:721-33. 2001
    ..This review deals with our understanding to date of how mutations in the APC gene translate into changes at the protein level, which in turn contribute to the role of APC in tumorigenesis...
  56. pmc The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster
    T B Chou
    Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genetics 144:1673-9. 1996
    ..In this paper we have built chromosomes that allow the use of this technique to the autosomes. We describe the various steps involved in the development of this technique as well as the properties of the chromosomes utilized...
  57. ncbi Gastric cancer: new genetic developments
    Henry T Lynch
    Department of Preventive Medicine, Creighton University School of Medicine, Omaha, Nebraska 68178, USA
    J Surg Oncol 90:114-33; discussion 133. 2005
    ..This paper reviews the genetics of both intestinal and diffuse types of gastric carcinoma, their differential diagnosis, molecular genetics, pathology, and, when known, their mode of genetic transmission within families...
  58. ncbi Clinical case seminar: in vivo and in vitro characterization of a novel germline RET mutation associated with low-penetrant nonaggressive familial medullary thyroid carcinoma
    Leonardo D'Aloiso
    Unit of Endocrinology and Division of Anatomic Pathology, Istituto di Ricovero e Cura a Carattere Scientifico Csa Sollievo della Sofferenza Hospital, Foggia, Italy
    J Clin Endocrinol Metab 91:754-9. 2006
    ..RET mutation analysis provides useful information on the clinical outcome of medullary thyroid carcinomas (MTCs) and the risk of disease in the family members...
  59. ncbi Biological basis of germline mutation: comparisons of spontaneous germline mutation rates among drosophila, mouse, and human
    J B Drost
    Institute for Mutagenesis, Louisiana State University, Baton Rouge 70803 1725, USA
    Environ Mol Mutagen 25:48-64. 1995
  60. ncbi The role of hMLH3 in familial colorectal cancer
    Hong Xu Liu
    Department of Thoracic Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, People s Republic of China
    Cancer Res 63:1894-9. 2003
    ..None of the tumors with hMLH3 mutations showed microsatellite instability, which demonstrates that hMLH3 does not make its contribution to carcinogenesis through an impaired DNA mismatch repair function...
  61. ncbi Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers
    Duan Jun Tan
    Department of Oncology, Georgetown University Medical Center, Washington, DC 20057 1477, USA
    Genes Chromosomes Cancer 37:186-94. 2003
    ..More extensive biochemical and molecular studies will be necessary for determining the pathologic effect of these somatic mutations...
  62. ncbi Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma
    B E Baysal
    Department of Psychiatry, The University of Pittsburgh Medical Center, Pittsburgh, PA 15213 2593, USA
    Science 287:848-51. 2000
    ..These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology...
  63. ncbi Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas
    Diana E Benn
    Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Syney, NSW, Australia
    Oncogene 22:1358-64. 2003
    ..Therefore, we conclude that SDHB has a major role in the pathogenesis of familial phaeochromocytomas, but the possible role of SDHB in sporadic tumours showing allelic loss at 1p36 has yet to be ascertained...
  64. pmc Low frequency of germline E-cadherin mutations in familial and nonfamilial gastric cancer
    J Stone
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK
    Br J Cancer 79:1935-7. 1999
    ..No pathogenic mutations were observed in any of the 106 patients. The results indicate that germline mutations in E-cadherin will not account for more than 3% of gastric cancers...
  65. pmc APC gene: database of germline and somatic mutations in human tumors and cell lines
    P Laurent-Puig
    Hôpital Laennec Service de Chirurgie Digestive Générale et Oncologique, 42 rue de Sevres, 75007 Paris, France
    Nucleic Acids Res 26:269-70. 1998
    ..It includes both molecular information about the mutations and clinical data about the patients. Software has been designed to analyse all this information in the database...
  66. ncbi Drastic genetic instability of tumors and normal tissues in Turcot syndrome
    M Miyaki
    Department of Biochemistry, The Tokyo Metropolitan Institute of Medical Science, Japan
    Oncogene 15:2877-81. 1997
    ..Additional unknown germline mutation may contribute to the genetic instability in normal tissues...
  67. ncbi Germline mutations in HRAS proto-oncogene cause Costello syndrome
    Yoko Aoki
    Department of Medical Genetics, Tohoku University School of Medicine, 1 1 Seiryo machi, Sendai 980 8574, Japan
    Nat Genet 37:1038-40. 2005
    ..Our observations suggest that germline mutations in HRAS perturb human development and increase susceptibility to tumors...
  68. ncbi Single-molecule PCR analysis of germ line mutation induction by anticancer drugs in mice
    Colin D Glen
    Department of Genetics and Medical Research Council Toxicology Unit, University of Leicester, Leicester, United Kingdom
    Cancer Res 68:3630-6. 2008
    ..mutagens and anticancer drugs in humans requires the development of efficient systems for monitoring germ line mutation. The suitability of a single-molecule PCR-based approach for monitoring mutation induction at the mouse ..
  69. ncbi Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome
    H Nakagawa
    Department of Clinical Genetics, Biomedical Research Center, Osaka University, Japan
    Hum Genet 103:168-72. 1998
  70. pmc Germline mutations of the E-cadherin(CDH1) and TP53 genes, rather than of RUNX3 and HPP1, contribute to genetic predisposition in German gastric cancer patients
    G Keller
    Institute of Pathology, Klinikum rechts der Isar, Technische Universitat Munchen, Germany
    J Med Genet 41:e89. 2004
  71. ncbi Genomic rearrangements in the BRCA1 and BRCA2 genes
    Sylvie Mazoyer
    Laboratoire de Génétique UMR5201 CNRS, Universite Claude Bernard Lyon 1, Lyon, France
    Hum Mutat 25:415-22. 2005
    ..The principal mechanisms that are thought to lead to their formation, founder effects, and recombination hotspots, are also discussed...
  72. ncbi Bethesda guidelines: relation to microsatellite instability and MLH1 promoter methylation in patients with colorectal cancer
    J Raedle
    Second Department of Internal Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt am Main, Germany
    Ann Intern Med 135:566-76. 2001
    ..The Bethesda guidelines were established to identify patients with colorectal cancer who should be tested for microsatellite instability...
  73. ncbi Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia
    Marianthi Georgitsi
    Department of Medical Genetics, University of Helsinki, Finland
    J Clin Endocrinol Metab 92:3321-5. 2007
    ..Recently, a germline mutation in the CDKN1B gene, encoding p27(Kip1), was reported in one suspected MEN1 family with two acromegalic patients...
  74. pmc The BRCA2 gene product functionally interacts with p53 and RAD51
    L Y Marmorstein
    The Derald H Ruttenberg Cancer Center, The Mount Sinai Medical Center, One Gustave L Levy Place, New York, NY 10029, USA
    Proc Natl Acad Sci U S A 95:13869-74. 1998
    ..These findings demonstrate that BRCA2 physically and functionally interacts with two key components of cell cycle control and DNA repair pathways. Thus, BRCA2 likely participates with p53 and RAD51 in maintaining genome integrity...
  75. ncbi Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer
    Melissa C Southey
    Genetic Epidemiology Laboratory, Department of Pathology, Australia
    J Clin Oncol 23:6524-32. 2005
    ..The relationships between mismatch repair (MMR) protein expression, microsatellite instability (MSI), family history, and germline MMR gene mutation status have not been studied on a population basis...
  76. ncbi Drug resistance caused by reversion mutation
    Alan Ashworth
    The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London, United Kingdom
    Cancer Res 68:10021-3. 2008
    ..Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer...
  77. ncbi Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation
    O Gimm
    Translational Research Laboratory, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    J Clin Endocrinol Metab 82:3902-4. 1997
    ..Our data demonstrate a novel etiologic event which may have roles in predisposition to MEN 2B when present in the germline and in the pathogenesis of sporadic MTC when somatic...
  78. ncbi High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing
    Frederieke M Brouwers
    Section of Medical Neuroendocrinology, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892 1109, USA
    J Clin Endocrinol Metab 91:4505-9. 2006
    ..Mutations of the gene for succinate dehydrogenase subunit B (SDHB) are associated with a high risk of malignancy, but establishing the precise contribution requires relatively large numbers of patients with well-defined malignancy...
  79. ncbi BRCA1 and BRCA2 mutations in women from Shanghai China
    Nicola M Suter
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Cancer Epidemiol Biomarkers Prev 13:181-9. 2004
    ..Most alterations observed appear unique to the Chinese population, suggesting a resource that will be useful for assessing risk among both Chinese women and United States women of Chinese descent...
  80. ncbi Refining the relation between 'first hits' and 'second hits' at the APC locus: the 'loose fit' model and evidence for differences in somatic mutation spectra among patients
    Michael Crabtree
    Molecular and Population Genetics Laboratory, Cancer Research UK, 44, Lincoln s Inn Fields, London WC2A 3PX, UK
    Oncogene 22:4257-65. 2003
  81. pmc Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes
    X P Zhou
    Clinical Cancer Genetics and Human Cancer Genetics Programs, Comprehensive Cancer Center, and the Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
    Am J Hum Genet 69:704-11. 2001
    ..Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype...
  82. ncbi Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency
    N A Alam
    Molecular and Population Genetics Laboratory, Cancer Research UK, Lincoln s Inn Fields, London WC2A 3PX, UK
    Hum Mol Genet 12:1241-52. 2003
  83. ncbi Role of VHL gene mutation in human cancer
    William Y Kim
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Clin Oncol 22:4991-5004. 2004
    ..On the other hand, clear genotype-phenotype correlations are emerging in VHL disease and can be rationalized if pVHL has functions separate from its control of HIF...
  84. ncbi Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC)
    A Loukola
    Department of Medical Genetics, Biomedicum Helsinki, FIN-00014 University of Helsinki, Finland
    Cancer Res 61:4545-9. 2001
    ..BAT26 was able to identify all 27 mutation-positive individuals in this series. The marker failed to identify 2 high MSI tumors and 20 low MSI tumors, all of which expressed MLH1, MSH2, and MSH6 when scrutinized by immunohistochemistry...
  85. ncbi BRCA1 promoter region hypermethylation in ovarian carcinoma: a population-based study
    R L Baldwin
    Division of Gynecologic Oncology, The Burns and Allen Research Institute Cedars Sinai Medical Center, Los Angeles, California 90048 USA
    Cancer Res 60:5329-33. 2000
  86. ncbi E-cadherin germline mutations in familial gastric cancer
    P Guilford
    Cancer Genetics Laboratory, Biochemistry Department, University of Otago, Dunedin, Aotearoa New Zealand
    Nature 392:402-5. 1998
    ..These results describe, to our knowledge for the first time, a molecular basis for familial gastric cancer, and confirm the important role of E-cadherin mutations in cancer...
  87. ncbi A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family
    J A Randerson-Moor
    ICRF Genetic Epidemiology Division, ICRF Clinical Centre in Leeds, Cancer Genetics Building, St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK
    Hum Mol Genet 10:55-62. 2001
  88. ncbi E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer
    P J Guilford
    Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin, New Zealand
    Hum Mutat 14:249-55. 1999
    ..These results demonstrate that germline mutation of the E-cadherin gene is a common cause of hereditary diffuse gastric cancer and suggest a role for these mutations in the incidence of breast cancer...
  89. ncbi Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil
    Edenir Inez Palmero
    Post Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Brazil
    Cancer Lett 261:21-5. 2008
  90. ncbi Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors
    A H S Gylling
    Department of Medical Genetics, University of Helsinki, Helsinki, Finland
    Carcinogenesis 29:1351-9. 2008
    ..Uroepithelial cancers of the ureter (and bladder to lesser extent) share many characteristics of MMR deficiency-driven tumorigenesis, whereas brain tumors and kidney adenocarcinomas follow separate pathways...
  91. ncbi Transforming ability of MEN2A-RET requires activation of the phosphatidylinositol 3-kinase/AKT signaling pathway
    C Segouffin-Cariou
    Laboratoire de Genetique, CNRS UMR 5641, Domaine Rockefeller, 8 avenue Rockefeller, 69373 Lyon, Cedex 08, France
    J Biol Chem 275:3568-76. 2000
    ..In summary, these data are consistent with the notion that RET-mediated cell-transforming effect is critically dependent on the activation of the PI3K/AKT pathway...
  92. ncbi Analysis of BRCA1 and BRCA2 in breast and breast/ovarian cancer families shows population substructure in the Iberian peninsula
    A Vega
    Unidad de Medicina Molecular, Hospital de Conxo Universidad de Santiago de Compostela, Spain
    Ann Hum Genet 66:29-36. 2002
    ..The BRCA1 330 A>G mutation was found in four unrelated families and accounted for 50% of all identified mutations...
  93. ncbi Strong male-driven evolution of DNA sequences in humans and apes
    Kateryna D Makova
    Department of Ecology and Evolution, University of Chicago, IL 60637, USA
    Nature 416:624-6. 2002
    ..Moreover, we provide an explanation for the small estimate of alpha in a previous study. Our study reinstates a high alpha in hominoids and supports the view that DNA replication errors are the primary source of germline mutation...
  94. ncbi Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer
    Kaspar Truninger
    Institute of Molecular Cancer Research, University of Zurich, Switzerland
    Gastroenterology 128:1160-71. 2005
    ..The protein encoded by PMS2 is also essential for MMR; however, alterations in this gene have been documented only in extremely rare cases. We addressed this unexpected finding by analyzing a large series of CRCs...
  95. ncbi Relative frequency and morphology of cancers in STK11 mutation carriers
    Wendy Lim
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
    Gastroenterology 126:1788-94. 2004
    ..There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS)...
  96. 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
  97. pmc Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation
    G Keller
    Institute of Pathology, Department of Surgery, Technische Universitat Munchen, Munich, Germany
    Am J Pathol 155:337-42. 1999
    ..Thus, our finding suggests that besides diffuse type gastric cancer, lobular breast carcinomas may be associated with germline CDH1 mutations...
  98. ncbi Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred
    Carla Oliveira
    Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison MRC Research Centre, Addenbrooke s Hospital, Cambridge, UK
    Hum Mutat 19:510-7. 2002
    ..These results add support to the evidence that only HDGC families harbor germline mutations in CDH1 and that genes other than CDH1 remain to be identified...
  99. ncbi A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth
    G Denning
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
    Oncogene 26:3930-40. 2007
    ..We propose that nuclear localization of PTEN is not compatible with plasma membrane-targeted growth suppressive functions of PTEN...
  100. pmc Genetic mechanisms in Apc-mediated mammary tumorigenesis
    Mari Kuraguchi
    Harvard Partners Center for Genetics and Genomics, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Genet 5:e1000367. 2009
  101. ncbi Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia
    S C Lee
    Department of Haematology Oncology, National University Hospital, Singapore
    Clin Genet 68:137-45. 2005
    ..Distinct clinical and molecular characteristics were identified among Asian HNPCC kindreds and may have important clinical implications...

Research Grants63

  1. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
  2. Role of Bone Morphogenetic Protein 4 in Hypoxic Pulmomary Hypertension
    Jian Wang; Fiscal Year: 2013
    ..Our study focuses on investigation of whether and how BMP4 regulates this process, which, if successful, will lead to improved methods of pharmacological prevention and treatment of this lethal complication of chronic lung diseases. ..
  3. The Role of RAS/MAPK Signaling in Alveolar Process Development
    Amnon Sharir; Fiscal Year: 2013
  4. Germline KLLN Alterations in PTEN Mutation Negative Cowden Syndrome
    EMILY ALISON NIZIALEK; Fiscal Year: 2013
  5. Mutational and evolutionary impact of mitochondrial dysfunction
    SUZANNE R ESTES; Fiscal Year: 2013
    ..Understanding the fundamental properties of mutation is of central importance to understanding its role in diverse genetic disorders, cancers and the aging process. ..
  6. Curcumin chemoprevention in familial adenomatous polyposis
    Francis M Giardiello; Fiscal Year: 2013
    ..abstract_text> ..
  7. The Role of Germline Mutation and Parental Age in Autism Spectrum Disorders
    Jonathan Sebat; Fiscal Year: 2013
    ..We will identify genes that confer significant risk for autism, and we will determine how intrinsic properties of the genome interact with extrinsic forces to determining risk for disease in offspring. ..
  8. Regulation of NEMO modifications in radiation-induced NF-kB signaling
    Shigeki Miyamoto; Fiscal Year: 2013
    ..Second, understanding the mechanisms of NF-kB activation by DNA damaging agents may help identify novel drug targets to improve the current methods of cancer therapy. ..
  9. Studies of the role of microRNA miR-16-1 in the NZB mouse model of CLL
    Elizabeth S Raveche; Fiscal Year: 2012
    ..The overall outcome of these studies will be to determine the potential efficacy of miR- 15a/16 delivery as a therapy or an adjuvant to chemotherapy in CLL. ..
  10. Investigations on the role of the CDK8 oncogene in colon cancer
    William C Hahn; Fiscal Year: 2013
    ..These biochemical, cell and chemical biological studies will not only provide insight into the biology of this kinase oncogene but will serve as a foundation for translational studies for the development of novel therapeutic agents. ..
  11. Analysis of the Role of Ras Signaling in Amelogenesis
    ..In addition, exploring the effect of Ras on ameloblast cell polarity will further reveal the general role of Ras in epithelial cell polarity. ..
  12. Validation and Extension of the PREMM Model for Inherited Colorectal Cancer
    Sapna Syngal; Fiscal Year: 2013
  13. Targeted Approach for Prevention and Therapy of Colorectal Cancer
    Vincent W Yang; Fiscal Year: 2013
    ..The intent of this effort is to obtain well-tolerated, long-lived bioavailable compounds suitable for therapeutic use in colorectal cancer. ..
  14. Time-Course Proteomics to Uncover the Mechanism and Nature of Aging in C. elegans
    JARRETT DAVID EGERTSON; Fiscal Year: 2013
    ..An understanding of this mechanism could open the door to new methods of studying and slowing human aging. ..
  15. Germline and Somatic Genetic Changes in Pulmonary Arterial Hypertension
    Micheala A Aldred; Fiscal Year: 2013
    ..The long term aims are to better understand what causes pulmonary hypertension and who is most at risk, in order to refine therapeutic interventions and work towards prevention of the disease. ..
  16. Genome instability and epigenetic deregulation in retinoblastoma and osteosarcoma
    ..The use integrative analyses of the changes in chromatin organization and gene expression that occur during tumorigenesis will help us identify potential novel therapeutic targets for anticancer treatment. ..
    Deborah Schrag; Fiscal Year: 2003
    ..abstract_text> ..
    Steve Sommer; Fiscal Year: 1999
    ..factor IX gene in eight great apes and Old World monkeys the same in each lineage?; and (viii) Are the amino acids conserved in factor IX during nonmammalian evolution the same amino acids that are mutated in humans with hemophilia B? ..
  19. Screening Pretest for HNPCC
    Jeremy Fields; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
    SABINE LOEW; Fiscal Year: 2000
    ..Specifically, germ line mutation rates will be estimated by determining novel minisatellite fragments in deer mouse progeny for mouse ..
  21. A Schizosaccharomyces pombe Model of Birt-Hogg-Dube Syndrome
    ELIZABETH HENSKE; Fiscal Year: 2007
    ..Nothing is currently known about how BHD gene mutations lead to human disease. We will use a novel yeast model of BHD to elucidate the function of the BHD protein. ..
    Paula Clemens; Fiscal Year: 2003
    Greta Bunin; Fiscal Year: 2005
    ..Sporadic heritable RBL is a childhood cancer worth studying in its own right and an ideal model for the investigation of new germline mutation. ..
  24. The Familial Colorectal Neoplasia Collaborative Group
    Alfonso Bellacosa; Fiscal Year: 2002
    ..These studies may provide new insights into the mechanisms of eukaryotic mismatch repair and further the link between defective DNA repair and cancer. ..
  26. A novel mutation in the T8 microsatellite of 3-UTR CDK2-AP1 gene in MSI CRC
    Thomas Weber; Fiscal Year: 2007
    ..At the completion of this proposed pilot study, will urther determine del T alteration in a large number of CRC patients to identify high risk population. [unreadable] [unreadable] [unreadable]..
  27. Biology of CHK2 Kinase In Lung Cancer
    Weixin Wang; Fiscal Year: 2005
    Raymond DuBois; Fiscal Year: 2002
    ..3) Characterize two genes (X-7 and X-18) which lead to upregulation of COX-2 expression when they are somatically mutated in RIE-1 cells. ..
    INDRANI BAGCHI; Fiscal Year: 2004
    ..To determine the functional role of ERG1 during early pregnancy, mice harboring a targeted germ line mutation of ERG1 will be developed and analyzed for potential reproductive phenotypes, such as impairment in embryo ..
    Antonio Baldini; Fiscal Year: 2003
    ..Developmental problems of the pharyngeal apparatus underlie many birth defects, including relatively common craniofacial and cardiovascular abnormalities. ..
    Kenneth Kemphues; Fiscal Year: 2005
    Henry Lynch; Fiscal Year: 2004
    ZAKI SHERIF; Fiscal Year: 2004
    ..These studies of LFS should delineate the correlation between genotype and phenotype in LFS and contribute to the general understanding of the processes leading to carcinogenesis. ..
  34. Real-Time Imaging of Hypoxia based on VHL Activity
    William Kaelin; Fiscal Year: 2004
    ..Such mice could be used to study diseases characterized by the presence of hypoxic cells, such as cancer, and could also be used to monitor pharmacodynamic effects of agents that alter tissue oxygenation and/or modulate HIF. ..
    TIMOTHY BYRNE; Fiscal Year: 1999
    ..A sensitivity of greater than 75 percent would establish a basis for further development of this assay as a noninvasive, cost effective screening test for male and female carriers of BRCA1 mutations. ..
  36. Role of CDK4 in Cell Cycle Progression and Cancer
    E Reddy; Fiscal Year: 2006
    Patrick Lynch; Fiscal Year: 2000
    ..In addition, a number of ancillary evaluations will examine the relative impact of this potential preventive approach on the psychosocial status of patients. ..
  38. Somatic Mutation in Cerebral Cavernous Malformations
    Judith Gault; Fiscal Year: 2009
    ..This proposal will develop new methods of somatic mutation detection and provide evidence of somatic mutation involvement in a common genetic disease, cerebral cavernous malformations, that predisposes to stroke and epilepsy. ..
    Sapna Syngal; Fiscal Year: 2004
    ..Evidence that MSH6 is a moderately penetrant, later-onset hereditary colorectal cancer gene would imply the existence of similar genes for other common cancers that await discovery. ..
  40. The Microsatellite Instability Phenotype
    MICHAEL SICILIANO; Fiscal Year: 2007
    ..Finally, we intend to determine the impact of inherited organism-dominant/cell recessive germline mutations on future generations. ..
  41. Pharmacogenetic Epidemiology of Birth Defects and Cancer
    Timothy Rebbeck; Fiscal Year: 2004
    Monica Bertagnolli; Fiscal Year: 2001
    ..Finally, we will apply this information to a study of NSAID-induced tumor regression in humans with Familial Adenomatous Polyposis, a condition characterized by germline mutation of the APC gene. ..
  43. The Molecular Basis of Juvenile Polyposis
    James Howe; Fiscal Year: 2005
    ..These studies will also benefit JP patients by improving presymptomatic genetic testing, and identification of new therapeutic targets for polyp regression and cancer prevention in JP. ..
  44. Regulation of SMAD4 and BMPR1A Expression in Juvenile Polyposis
    James R Howe; Fiscal Year: 2010
    ..abstract_text> ..
  45. In Vivo Studies of TSC-Related Tumorigenesis
    Raymond Yeung; Fiscal Year: 2008
    ..Our long-term goal is to exploit the mechanisms of these pathways in the development of clinical therapy for TSC-related disorders. ..
    Raymond Yeung; Fiscal Year: 2004
    ..Appreciation of these 'modifier' genes will impart new knowledge about the interplay between genes and environment during the development of complex diseases such as cancer. ..
  47. Characterization of the Chromosome 17q23 Amplicon
    Fergus Couch; Fiscal Year: 2006
    ..Thus, the project may involve a complete transition from benchtop to bedside. Finally, the amplified and overexpressed genes may prove useful as important targets of gene, pharmacological, and immunological therapy in the future. ..
  48. Development of Statistical Approaches Allowing for Genetic Covariates
    Chih Chieh Wu; Fiscal Year: 2008
    ..The Texas Cancer Genetic Consortium, a Cancer Genetic Network regional center, will provide the breast cancer data. [unreadable] [unreadable] [unreadable]..
    Fergus Couch; Fiscal Year: 2002
    CHRISTI WALTER; Fiscal Year: 2001
    ..This study will advance an understanding of the fundamental mechanisms involved in mutagenesis in germ cells. ..
  51. Base Excision Repair, Genetic Integrity & Health Span
    CHRISTI WALTER; Fiscal Year: 2008
    ..Genetic integrity, apoptosis, and pathology will be examined using a variety of molecular, biochemical and cell biological approaches. ..
    Noralane Lindor; Fiscal Year: 2007
    ..fs20\par \par } ..
  53. Germ Cell Aging
    CHRISTI WALTER; Fiscal Year: 2007
    ..This study will advance our understanding of the fundamental mechanisms involved in male germline integrity. ..
    Eric Hall; Fiscal Year: 2001
  55. 1st Costello Syndrome Symposium
    KATHERINE RAUEN; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  56. TLR4 as an LPS sendor and susceptibility locus
    Bruce Beutler; Fiscal Year: 2007
    ..The new mutations that are found--and those that have already been found in preliminary efforts--will be isolated by positional cloning. ..
  57. Structural, Computational and Epidemiologic Analyses of*
    Noah Kauff; Fiscal Year: 2006
    ..abstract_text> ..
    Stephen Gruber; Fiscal Year: 2008
    ..abstract_text> ..
  59. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2006
    ..Fourth, circumvention of the toleragenic mechanism might be used to prevent normal gestation, leading to termination of pregnancy within a few days following implantation of the blastocyst. ..
  60. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2006
    ..In the case of mutations that abolish LPS tolerance, we will attempt to determine the net impact on host resistance to infection. ..
  61. Ovarian Cancer and Mismatch Repair Deficiency
    Tuya Pal; Fiscal Year: 2009
    ..abstract_text> ..
  62. Lipoprotein Metabolism 2008 Gordon Research Conference
    Robert Hegele; Fiscal Year: 2008
    ..End of Abstract) [unreadable] [unreadable] [unreadable]..
  63. Forward Genetic Analysis of the Innate Immune Contribution to MCMV Resistance
    Bruce Beutler; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..