MSH2

Summary

Gene Symbol: MSH2
Description: mutS homolog 2
Alias: COCA1, FCC1, HNPCC, HNPCC1, LCFS2, DNA mismatch repair protein Msh2, hMSH2, mutS homolog 2, colon cancer, nonpolyposis type 1
Species: human

Top Publications

  1. ncbi Characterization of MLH1 and MSH2 alternative splicing and its relevance to molecular testing of colorectal cancer susceptibility
    M Genuardi
    Istituto di Genetica Medica, Universita Cattolica del Sacro Cuore, Rome, Italy
    Hum Genet 102:15-20. 1998
  2. pmc Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics
    Sven Arnold
    Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Australia
    Hum Mutat 30:757-70. 2009
  3. pmc Mismatch recognition protein MutSbeta does not hijack (CAG)n hairpin repair in vitro
    Lei Tian
    Graduate Center for Toxicology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA
    J Biol Chem 284:20452-6. 2009
  4. ncbi Defective DNA mismatch repair in long-term (> or =3 years) survivors with pancreatic cancer
    John T Maple
    Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Pancreatology 5:220-7; discussion 227-8. 2005
  5. doi Mismatch repair gene mutations in Chinese HNPCC patients
    J Q Sheng
    Department of Gastroenterology, General Hospital of Beijing Military Region, Beijing, China
    Cytogenet Genome Res 122:22-7. 2008
  6. ncbi Tobacco use and increased colorectal cancer risk in patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome)
    Patrice Watson
    Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Neb, USA
    Arch Intern Med 164:2429-31. 2004
  7. pmc Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer
    Graham Casey
    Department of Cancer Biology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio 44195, USA
    JAMA 293:799-809. 2005
  8. pmc hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6
    S Acharya
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 93:13629-34. 1996
  9. ncbi Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes
    M Wehner
    Institute of Human Genetics, University of Bonn, Germany
    Hum Mutat 10:241-4. 1997
  10. ncbi Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review
    R J Mitchell
    Department of Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, United Kingdom
    Am J Epidemiol 156:885-902. 2002

Research Grants

  1. INHIBITION OF SPONTANEOUS MUTATION IN MISMATCH MUTATORS
    Catherine Klein; Fiscal Year: 2002
  2. INHERITED MSH6 MUTATIONS IN DIVERSE COLORECTAL CANCERS
    Sapna Syngal; Fiscal Year: 2004
  3. The Microsatellite Instability Phenotype
    MICHAEL SICILIANO; Fiscal Year: 2007
  4. Screening Pretest for HNPCC
    Jeremy Fields; Fiscal Year: 2007
  5. NEW HUMAN DNA REPAIR ENDONUCLEASE
    Alfonso Bellacosa; Fiscal Year: 2002
  6. Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention
    Roberd Bostick; Fiscal Year: 2009
  7. Sapna Syngal; Fiscal Year: 2016
  8. MOLECULAR GENETIC ALTERATIONS OF ENDOMETRIAL CARCINOMA
    LORA ELLENSON; Fiscal Year: 1999
  9. Gary M Kupfer; Fiscal Year: 2014
  10. ERIC E ALANI; Fiscal Year: 2016

Detail Information

Publications251 found, 100 shown here

  1. ncbi Characterization of MLH1 and MSH2 alternative splicing and its relevance to molecular testing of colorectal cancer susceptibility
    M Genuardi
    Istituto di Genetica Medica, Universita Cattolica del Sacro Cuore, Rome, Italy
    Hum Genet 102:15-20. 1998
    The phenomenon of alternative splicing in the DNA mismatch repair genes MLH1 and MSH2 was extensively investigated by coupled reverse transcription-polymerase chain reaction in different human tissues, including 42 mononuclear blood cell ..
  2. pmc Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics
    Sven Arnold
    Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Australia
    Hum Mutat 30:757-70. 2009
    ..Six programs were used to predict the effect of 13 MLH1 and 6 MSH2 gene variants on pre-mRNA splicing...
  3. pmc Mismatch recognition protein MutSbeta does not hijack (CAG)n hairpin repair in vitro
    Lei Tian
    Graduate Center for Toxicology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA
    J Biol Chem 284:20452-6. 2009
    ..Evidence presented here provides a novel view as to whether or not MutSbeta is involved in CAG repeat instability in humans...
  4. ncbi Defective DNA mismatch repair in long-term (> or =3 years) survivors with pancreatic cancer
    John T Maple
    Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Pancreatology 5:220-7; discussion 227-8. 2005
    ..To determine if long-term survival in pancreatic cancer could be attributed to defective DNA MMR, we ascertained its prevalence in 35 pancreatic cancer patients who survived > or =3 years after surgery...
  5. doi Mismatch repair gene mutations in Chinese HNPCC patients
    J Q Sheng
    Department of Gastroenterology, General Hospital of Beijing Military Region, Beijing, China
    Cytogenet Genome Res 122:22-7. 2008
    ..of DNA mismatch repair gene mutations in Chinese patients with hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome, the MLH1 and MSH2 genes from probands of 76 HNPCC families were sequenced...
  6. ncbi Tobacco use and increased colorectal cancer risk in patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome)
    Patrice Watson
    Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Neb, USA
    Arch Intern Med 164:2429-31. 2004
    ..variability in age at onset of colorectal cancer (CRC) in patients with hereditary nonpolyposis colorectal cancer (HNPCC) makes management decisions difficult...
  7. pmc Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer
    Graham Casey
    Department of Cancer Biology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio 44195, USA
    JAMA 293:799-809. 2005
    ..Current data suggest that mismatch repair mutations are highly heterogeneous and that many mutations are not detected when conventional DNA sequencing alone is used...
  8. pmc hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6
    S Acharya
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 93:13629-34. 1996
    The genetic and biochemical properties of three human MutS homologues, hMSH2, hMSH3, and hMSH6, have been examined...
  9. ncbi Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes
    M Wehner
    Institute of Human Genetics, University of Bonn, Germany
    Hum Mutat 10:241-4. 1997
  10. ncbi Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review
    R J Mitchell
    Department of Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, United Kingdom
    Am J Epidemiol 156:885-902. 2002
    Evidence to support a role for the mismatch repair genes human mutL homolog 1 (hMLH1) and human mutS homolog 2 (hMSH2) in the etiology of colorectal cancer has come from linkage analysis, segregation studies, and molecular biologic ..
  11. pmc Characterization of mutator pathway in younger-age-onset colorectal adenocarcinomas
    Seon Ae Roh
    Department of Surgery and Pathology, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Seoul, Korea
    J Korean Med Sci 18:387-91. 2003
    ..Microsatellite instability (MSI) occurs from the mutational inactivation of the DNA mismatch repair genes, i.e. hMSH2 and hMLH1 in HNPCC, as well as from epigenetic inactivation of hMLH1 in sporadic colorectal tumors...
  12. pmc Genetic detection of Chinese hereditary nonpolyposis colorectal cancer
    Long Cui
    Department of Colorectal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
    World J Gastroenterol 10:209-13. 2004
    To explore the germline mutations of the two main DNA mismatch repair genes (hMSH2 and hMLH1) between patients with hereditary non-polyposis colorectal cancer (HNPCC) and suspected (atypical) HNPCC.
  13. ncbi Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families
    Young Kyoung Shin
    Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, 110 744, Korea
    Hum Mutat 24:351. 2004
    Hereditary non-polyposis colorectal cancer (HNPCC), the most common hereditary colon cancer syndrome, is a dominant disorder caused by germline defects in mismatch repair (MMR) genes...
  14. pmc Clinicopathological and molecular genetic analysis of HNPCC in China
    Ding Cun Luo
    Department of Surgical Oncology, Second People s Hospital of Wenzhou, Wenzhou 325028, Zhejiang Province, China
    World J Gastroenterol 11:1673-9. 2005
    To explore the clinicopathological and molecular genetic features of hereditary nonpolyposis colorectal cancer (HNPCC) in Chinese population.
  15. ncbi hMutSbeta, a heterodimer of hMSH2 and hMSH3, binds to insertion/deletion loops in DNA
    F Palombo
    Istituto di Richerche di Biologia Molecolare P Angeletti Via Pontina Km 30, 600 I 00040 Pomezia Italy
    Curr Biol 6:1181-4. 1996
    ..Our data further suggest that hMSH3 and GTBP are redundant in loop repair, and help explain why only mutations in hMSH2, and not in GTBP or hMSH3, segregate with hereditary non-polyposis colorectal cancer (HNPCC) [7].
  16. ncbi The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch
    S Gradia
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Cell 91:995-1005. 1997
    ..Here we show that adenine nucleotide binding and hydrolysis by the human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch...
  17. ncbi Enhanced detection of deleterious and other germline mutations of hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds
    S Nomura
    Division of Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan
    Biochem Biophys Res Commun 271:120-9. 2000
    ..Here, we describe a novel and efficient approach for screening mutations of two major HNPCC susceptibility genes, hMSH2 and hMLH1...
  18. pmc MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation
    Yi Wang
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 100:15387-92. 2003
    ..We report that MSH2 (MutS homolog 2) protein interacts with the ATR (ATM- and Rad3-related) kinase to form a signaling module and ..
  19. ncbi Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms
    Jinru Shia
    Department of Pathology, Memorial Sloan Kettering, Cancer Center, New York, NY 10021, USA
    Am J Surg Pathol 29:96-104. 2005
    ..of persons with mutations in the DNA mismatch repair (MMR) genes in hereditary nonpolyposis colorectal cancer (HNPCC) remains to be defined...
  20. ncbi Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer
    Elisabeth Mangold
    Institute of Human Genetics, University Hospital Bonn, Germany
    Int J Cancer 116:692-702. 2005
    Mutations in DNA MMR genes, mainly MSH2 and MLH1, account for the majority of HNPCC, an autosomal dominant predisposition to colorectal cancer and other malignancies...
  21. pmc The nucleotide binding dynamics of human MSH2-MSH3 are lesion dependent
    Barbara A L Owen
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Nat Struct Mol Biol 16:550-7. 2009
    Here we report that the human DNA mismatch complex MSH2-MSH3 recognizes small loops by a mechanism different from that of MSH2-MSH6 for single-base mismatches. The subunits MSH2 and MSH3 can bind either ADP or ATP with similar affinities...
  22. ncbi Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer
    M Konishi
    Department of Biochemistry, Tokyo Metropolitan Institute of Medical Science, Japan
    Gastroenterology 111:307-17. 1996
    ..instability (replication error [RER]) is a characteristic of tumors in hereditary nonpolyposis colon cancer (HNPCC), but the mechanism of HNPCC carcinogenesis is not yet understood...
  23. ncbi MSH2 and MLH1 mutations in sporadic replication error-positive colorectal carcinoma as assessed by two-dimensional DNA electrophoresis
    Y Wu
    Department of Medical Genetics, University of Groningen, The Netherlands
    Genes Chromosomes Cancer 18:269-78. 1997
    ..In hereditary nonpolyposis colorectal cancer (HNPCC), RER is associated with defects in DNA mismatch repair genes...
  24. ncbi MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families
    H F Vasen
    Netherlands Foundation for the Detection of Hereditary Tumors, Leiden University Medical Centre
    J Clin Oncol 19:4074-80. 2001
    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers...
  25. ncbi The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer
    W S Samowitz
    Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
    Gastroenterology 121:830-8. 2001
    Estimates of the frequency of hereditary nonpolyposis colon cancer (HNPCC) based on clinical criteria have varied widely...
  26. ncbi HNPCC mutations in hMSH2 result in reduced hMSH2-hMSH6 molecular switch functions
    Christopher D Heinen
    Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Cancer Cell 1:469-78. 2002
    Mutations in the human mismatch repair (MMR) gene hMSH2 have been linked to approximately 40% of hereditary nonpolyposis colorectal cancers (HNPCC)...
  27. ncbi The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase
    Qin Yang
    Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bldg 37, Rm 3068, 37 Convent Drive, Bethesda, MD 20892 4255, USA
    Oncogene 23:3749-56. 2004
    ..mismatch repair components have been implicated in DNA homologous recombination repair, the exact function of hMSH2/6 in this pathway is unclear...
  28. ncbi Characterization of hMLH1 and hMSH2 gene dosage alterations in Lynch syndrome patients
    Linnea M Baudhuin
    Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Gastroenterology 129:846-54. 2005
    ..of Lynch syndrome cases are believed to be due to large genomic alterations in the mismatch repair genes hMLH1 and hMSH2. However, previous studies have not adequately identified the frequency and scope of such mutations, and routine ..
  29. ncbi Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study
    Jae Gahb Park
    Korean Hereditary Tumor Registry, Laboratory of Cell Biology, Cancer Research Institute and Cancer Research Center, Seoul National University College of Medicine, Korea
    Clin Cancer Res 12:3389-93. 2006
    The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC).
  30. ncbi Common variants in mismatch repair genes and risk of invasive ovarian cancer
    Honglin Song
    CR UK Department of Oncology, University of Cambridge Strangeways Research Laboratory, Cambridge, UK
    Carcinogenesis 27:2235-42. 2006
    ..Germline mutations in MMR genes are associated with hereditary non-polyposis colorectal cancer (HNPCC)...
  31. ncbi Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in Germany
    C Lamberti
    Department of Internal Medicine I, University of Bonn, Bonn, Germany
    Digestion 74:58-67. 2006
    Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC)...
  32. ncbi High proportion of large genomic rearrangements in hMSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families of the Basque Country
    Cristina Martinez-Bouzas
    Molecular Genetics Laboratory, Hospital de Cruces, Plaza de Cruces s n, 48903 Barakaldo Bizkaia, Spain
    Cancer Lett 255:295-9. 2007
    Hereditary nonpolyposis colorectal cancer (HNPCC), which represents the most common form of inherited colorectal cancer, results from germline alterations of the mismatch repair genes MSH2, MLH1 and MSH6...
  33. doi Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations
    E Barrow
    Department of General Surgery, Manchester Royal Infirmary, Manchester, UK
    Clin Genet 74:233-42. 2008
    Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition caused by inactivating mutations of DNA mismatch repair (MMR) genes...
  34. pmc Nuclear reorganization of DNA mismatch repair proteins in response to DNA damage
    Adam S Mastrocola
    Neag Comprehensive Cancer Center and Center for Molecular Medicine, University of Connecticut Health Center, 263 Farmington Avenue, ML3101, Farmington, CT 06030 3101, USA
    DNA Repair (Amst) 9:120-33. 2010
    ..Using synchronized populations of HeLa cells we demonstrated that hMSH2, hMLH1 and PCNA localize to the chromatin during S-phase, and accumulate to a greater extent in cells treated with ..
  35. pmc Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families
    Xu lin Wang
    Cancer Institute, The 2nd Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jie Fang Road, Hangzhou 310009, Zhejiang Province, China
    World J Gastroenterol 12:4074-7. 2006
    To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.
  36. ncbi hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds
    B Liu
    Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
    Cancer Res 54:4590-4. 1994
    ..We analyzed 29 HNPCC kindreds for mutations in the prototype DNA mismatch repair gene hMSH2 by a combination of linkage analysis, polymerase chain reaction-based screening, and sequencing of the coding ..
  37. ncbi The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer
    R Fishel
    Department of Microbiology and Molecular Genetics Markey Center for Molecular Genetics University of Vermont Medical School Burlington 05405
    Cell 75:1027-38. 1993
    We have identified a human homolog of the bacterial MutS and S. cerevisiae MSH proteins, called hMSH2. Expression of hMSH2 in E...
  38. ncbi A carboxy terminal domain of the hMSH-2 gene product is sufficient for binding specific mismatched oligonucleotides
    A Whitehouse
    Molecular Medicine Unit, St Jame s University Hospital, Leeds, United Kingdom
    Biochem Biophys Res Commun 225:289-95. 1996
    ..hMSH-2 is one of the hereditary non-polyposis colorectal cancer (HNPCC) tumor suppressor genes, and maps to human chromosome 2p16...
  39. ncbi Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer
    A Viel
    Division of Experimental Oncology I, Centro Riferimento Oncologico, Aviano, Italy
    Genes Chromosomes Cancer 18:8-18. 1997
    ..MLH1 are considered to be the two major genes that are responsible for hereditary nonpolyposis colorectal cancer (HNPCC)...
  40. ncbi Clinical findings with implications for genetic testing in families with clustering of colorectal cancer
    J T Wijnen
    Department of Human Genetics, Leiden University Medical Center, The Netherlands
    N Engl J Med 339:511-8. 1998
    Germ-line mutations in DNA mismatch-repair genes (MSH2, MLH1, PMS1, PMS2, and MSH6) cause susceptibility to hereditary nonpolyposis colorectal cancer...
  41. ncbi Mutator phenotypes of common polymorphisms and missense mutations in MSH2
    K Drotschmann
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Curr Biol 9:907-10. 1999
    Hereditary non-polyposis colorectal cancer (HNPCC) is associated with germline mutations in the DNA mismatch repair gene hMSH2 [1], the human homologue of the Escherichia coli MutS gene...
  42. ncbi Detection of mutations in mismatch repair genes in Portuguese families with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method approach
    P Fidalgo
    Gastroenterology Department, Instituto Portugues de Oncologia, Lisbon, Portugal
    Eur J Hum Genet 8:49-53. 2000
    Mutation searching was performed in the hMSH2 and hMLH1 genes in 20 Portuguese families representing 124 registered affected individuals...
  43. pmc Recurrent germline mutation in MSH2 arises frequently de novo
    D C Desai
    Division of Surgical Oncology, The Ohio State University, 410 W 10th Avenue, N 924 Doan Hall, Columbus, OH 43210, USA
    J Med Genet 37:646-52. 2000
    ..This mutation causes typical hereditary non-polyposis colorectal cancer (HNPCC) and has been observed in numerous probands and families world wide...
  44. ncbi HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLalpha and hMLH1-hEXO1 complexes
    A C Jäger
    Department of Clinical Biochemistry, Rigshospitalet, DK 2100 Copenhagen, Denmark
    Oncogene 20:3590-5. 2001
    Hereditary nonpolyposis colorectal cancer (HNPCC) is a common inherited form of neoplasia caused by germline mutations in DNA mismatch repair (MMR) genes...
  45. ncbi Molecular screening for hereditary nonpolyposis colorectal cancer: a prospective, population-based study
    A Percesepe
    Department of Internal Medicine, University of Modena, Modena, Italy
    J Clin Oncol 19:3944-50. 2001
    Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known...
  46. ncbi Activation of human MutS homologs by 8-oxo-guanine DNA damage
    Anthony Mazurek
    Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 277:8260-6. 2002
    ..containing a single 8-oxo-G on the DNA binding affinity, ATPase, and ADP right arrow ATP exchange activities of hMSH2-hMSH6 and hMSH2-hMSH3...
  47. ncbi Differential expression of the mismatch repair gene hMSH2 in malignant prostate tissue is associated with cancer recurrence
    Alfredo Velasco
    Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892 1501, USA
    Cancer 94:690-9. 2002
    ..instability (MSI) has been described in high-grade and lymph node positive prostate carcinoma specimens, an analysis comparing hMSH2 expression, MSI, and outcome in clinically organ confined prostate carcinoma has not been reported.
  48. pmc Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene
    Anja Wagner
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Am J Hum Genet 72:1088-100. 2003
    The identification of germline mutations in families with HNPCC is hampered by genetic heterogeneity and clinical variability...
  49. ncbi Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA
    C F Taylor
    Cancer Research UK Mutation Detection Facility, St James University Hospital, Leeds, UK
    Hum Mutat 22:428-33. 2003
    ..on the basis of a family history consistent with autosomal dominant hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) were tested by MLPA...
  50. ncbi A defined human system that supports bidirectional mismatch-provoked excision
    Leonid Dzantiev
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 15:31-41. 2004
    ..By contrast, RFC and PCNA have only a limited effect on 5' to 3' excision directed by a 5' strand break...
  51. ncbi Genotyping possible polymorphic variants of human mismatch repair genes in healthy Korean individuals and sporadic colorectal cancer patients
    Jin C Kim
    Department of Surgery, University of Ulsan College of Medicine, and Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, 388 1 Poongnap 2 Dong Songpa Ku, Seoul 138 736, Korea
    Fam Cancer 3:129-37. 2004
    ..Of these 27 variants, 4 (hMSH2 gIVS12-6, hMLH1 655, hMLH1 1151, and hMSH2 1168, in descending order) were identified as SNPs occurring in 4...
  52. ncbi hMutS alpha is protected from ubiquitin-proteasome-dependent degradation by atypical protein kinase C zeta phosphorylation
    Hélène Hernandez-Pigeon
    INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr Baylac, CHU Purpan, BP 3028, 31024 Toulouse Cedex 3, France
    J Mol Biol 348:63-74. 2005
    The hMutS alpha (hMSH2-hMSH6) protein heterodimer plays a critical role in the detection of DNA mispairs in the mismatch repair (MMR) process...
  53. ncbi The 5' region of the MSH2 gene involved in hereditary non-polyposis colorectal cancer contains a high density of recombinogenic sequences
    Françoise Charbonnier
    Inserm U614 IFRMP, Faculty of Medicine, Rouen, France
    Hum Mutat 26:255-61. 2005
    MSH2 rearrangements are involved in approximately 10% of hereditary non-polyposis colorectal cancer (HNPCC) families, and in most of the rearrangements, exon 1 is deleted...
  54. ncbi Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants
    Constanze Pagenstecher
    Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany
    Hum Genet 119:9-22. 2006
    ..outside the highly conserved splicing region are often found in hereditary nonpolyposis colorectal cancer (HNPCC) families...
  55. ncbi Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer
    S Demokan
    Oncology Institute, Department of Basic Oncology, Istanbul Medical Faculty, Department of Otorhinolaryngology, Istanbul University, Turkey
    Ann Oncol 17:995-9. 2006
    Methylation in the promoter region of the DNA mismatch repair genes hMLH1 and hMSH2 and microsatellite instability at three loci were analyzed in the tumor tissue from patients with head and neck cancer.
  56. pmc Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer
    R C Niessen
    Department of Gastroenterology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
    Gut 55:1781-8. 2006
    Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations.
  57. pmc In silico and in vivo splicing analysis of MLH1 and MSH2 missense mutations shows exon- and tissue-specific effects
    Patrizia Lastella
    Section of Medical Genetics, Department of Biomedicine in Childhood, University of Bari, Italy
    BMC Genomics 7:243. 2006
    ..Therefore we aimed to verify how predictions that can be drawn from in silico analysis correlate with results obtained in an in vivo splicing assay...
  58. ncbi Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal cancer in a Chinese population
    Yimei Fan
    Department of Medical Genetics, Medical School, Nanjing University, Nanjing, China
    Cancer Genet Cytogenet 170:121-8. 2006
    Epidemiologic, structural, and bioinformatic analyses were used to evaluate variants in the MSH2 and MLH1 genes in 187 subjects with suspected hereditary gastrointestinal cancer in China...
  59. ncbi Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics
    Kristina Lagerstedt Robinson
    Department of Clinical Genetics, Karolinska University Hospital, S 17176 Stockholm, Sweden
    J Natl Cancer Inst 99:291-9. 2007
    ..In particular, patients with Lynch syndrome, hereditary nonpolyposis colorectal cancer (HNPCC), have an increased risk to develop colorectal cancer at an early age...
  60. pmc A mononucleotide markers panel to identify hMLH1/hMSH2 germline mutations
    M Pedroni
    Department of Medicine and Medical Specialities, University of Modena and Reggio Emilia, Modena, Italy
    Dis Markers 23:179-87. 2007
    ..testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations...
  61. ncbi Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC)
    Johanne Geary
    Department of Medical Genetics, St George s University of London, Cranmer Terrace, London SW17 0RE, UK
    Fam Cancer 7:163-72. 2008
    The family histories of 130 individuals with documented hereditary non-polyposis colorectal cancer (HNPCC) (caused by mutations in mismatch-repair (MMR) genes MSH2 (n = 64), MLH1 (n = 62) or MSH6 (n = 4)) were obtained, and incidence of ..
  62. pmc Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer
    Hei ying Jin
    National Center of Colorectal Surgery, 3rd Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 1 Jinling Road, Nanjing 210001, China
    BMC Cancer 8:44. 2008
    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC...
  63. doi Origins and prevalence of the American Founder Mutation of MSH2
    Mark Clendenning
    Human Cancer Genetics Program, The Ohio State University, Columbus, Ohio 43210, USA
    Cancer Res 68:2145-53. 2008
    Large germline deletions within the mismatch repair gene MSH2 account for a significant proportion (up to 20%) of all deleterious mutations of this gene which are associated with Lynch syndrome...
  64. pmc The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population
    Lise Lotte Christensen
    Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark
    BMC Med Genet 9:52. 2008
    Mutations in the mismatch repair genes hMLH1 and hMSH2 predispose to hereditary non-polyposis colorectal cancer (HNPCC)...
  65. doi A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects
    Isabelle Tournier
    INSERM U614, Federate Institute for Multidisciplinary Research on Peptides, Faculty of Medicine, University of Rouen, Department of Genetics and Institute for Biomedical Research, Rouen University Hospital, Rouen, France
    Hum Mutat 29:1412-24. 2008
    ..have been found in the mismatch repair genes MLH1 and MSH2 involved in hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome)...
  66. doi Mechanisms of pathogenicity in human MSH2 missense mutants
    Saara Ollila
    Department of Biological and Environmental Sciences, Genetics, University of Helsinki, Helsinki, Finland
    Hum Mutat 29:1355-63. 2008
    ..mismatch repair (MMR) gene MSH2 is the second most frequently mutated hereditary nonpolyposis colorectal cancer (HNPCC) susceptibility locus...
  67. pmc Characterization of a highly conserved binding site of Mlh1 required for exonuclease I-dependent mismatch repair
    Claudine Dherin
    CEA, IRCM, UMR217, Radiobiologie Moléculaire et Cellulaire, Fontenay aux Roses, France
    Mol Cell Biol 29:907-18. 2009
    ..Given the conservation of Mlh1 and Exo1 interaction, it may readily impact Mlh1-dependent functions such as cancer prevention in higher eukaryotes...
  68. doi Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1
    Marjolijn J L Ligtenberg
    Department of Human Genetics 849, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 41:112-7. 2009
    ..to colorectal and endometrial cancers owing to inactivating germline mutations in mismatch repair genes, including MSH2 (ref. 1)...
  69. pmc Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair
    Ankita Shahi
    DNA Repair Research Center, Department of Pharmacology, Chosun University School of Medicine, 375 Seosuk dong, Gwangju, 501 759, South Korea
    Nucleic Acids Res 39:2130-43. 2011
    MSH6, a key component of the MSH2-MSH6 complex, plays a fundamental role in the repair of mismatched DNA bases. Herein, we report that MSH6 is a novel Ku70-interacting protein identified by yeast two-hybrid screening...
  70. doi Immunohistochemical analysis of p53, APE1, hMSH2 and ERCC1 proteins in actinic cheilitis and lip squamous cell carcinoma
    Ludmilla R Souza
    Health Science Programme, State University of Montes Claros, Montes Claros, MG, Brazil
    Histopathology 58:352-60. 2011
    This study has compared the tissue expression of the p53 tumour suppressor protein and DNA repair proteins APE1, hMSH2 and ERCC1 in normal, dysplastic and malignant lip epithelium.
  71. doi Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas
    Jörg Felsberg
    Department of Neuropathology, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
    Int J Cancer 129:659-70. 2011
    ..changes in the promoter methylation status and the expression of MGMT and the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 in pairs of primary and recurrent glioblastomas of 80 patients, including 64 patients treated with ..
  72. pmc Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops
    Walter H Lang
    Lawrence Berkeley National Laboratory, Life Sciences Division, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 108:E837-44. 2011
    ..Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics ..
  73. doi Human MutS and FANCM complexes function as redundant DNA damage sensors in the Fanconi Anemia pathway
    Min Huang
    Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, United States
    DNA Repair (Amst) 10:1203-12. 2011
    ..Here we show that the MutS homologs function in this capacity. A RNAi screen revealed that MSH2 silencing caused defective FA pathway activation, as assessed by damage-induced FANCD2 mono-ubiquitination...
  74. ncbi Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells
    J T Drummond
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Science 268:1909-12. 1995
    A mismatch-binding heterodimer of hMSH2 and a 160-kilodalton polypeptide has been isolated from HeLa cells by virtue of its ability to restore mismatch repair to nuclear extracts of hMSH2-deficient LoVo colorectal tumor cells...
  75. ncbi Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations
    R D Kolodner
    Division of Cell and Molecular Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115
    Genomics 24:516-26. 1994
    ..HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system...
  76. pmc Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing gradient-gel electrophoresis
    J Wijnen
    Department of Human Genetics, Sylvius Laboratory, Leiden University, The Netherlands
    Am J Hum Genet 56:1060-6. 1995
    Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common autosomal dominant cancer-susceptibility condition...
  77. ncbi Mutational analysis of the hMSH2 gene reveals a three base pair deletion in a family predisposed to colorectal cancer development
    J L Mary
    Department of Research, Kantonsspital, Basel, Switzerland
    Hum Mol Genet 3:2067-9. 1994
  78. ncbi Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer
    F S Leach
    Johns Hopkins Oncology Center, Baltimore, Maryland 21231
    Cell 75:1215-25. 1993
    Recent studies have shown that a locus responsible for hereditary nonpolyposis colorectal cancer (HNPCC) is on chromosome 2p and that tumors developing in these patients contain alterations in microsatellite sequences (RER+ phenotype)...
  79. ncbi CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations
    Y K Maliaka
    Department of Medical Genetics, Sechenov Moscow Medical Academy, Moscow, Russia
    Hum Genet 97:251-5. 1996
    ..The identification of the causative mutations in HNPCC families is desirable, since it confirms the diagnosis and allows the carrier status of unaffected relatives at ..
  80. ncbi Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer
    G Moslein
    Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
    Hum Mol Genet 5:1245-52. 1996
    ..have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colorectal cancer (HNPCC)...
  81. ncbi Use of SSCP analysis to identify germline mutations in HNPCC families fulfilling the Amsterdam criteria
    N E Beck
    Cancer Genetics and Immunology Laboratory, John Radeliffe Hospital, Headington, Oxford, Oxfordshire, UK
    Hum Genet 99:219-24. 1997
    Hereditary non-polyposis colorectal cancer (HNPCC) is a clinical syndrome characterised by an inherited predisposition to early onset colorectal and uterine cancers and an increased incidence of other cancers...
  82. pmc Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations
    J Wijnen
    MGC Department of Human Genetics, Medical Genetics Center, Leiden University, The Netherlands
    Am J Hum Genet 61:329-35. 1997
    Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant cancer-susceptibility condition characterized by early onset colorectal cancer...
  83. ncbi Novel germline mutations of hMSH2 in a patient with hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with six primary cancers
    S Okamura
    Department of Medical Genetics, Osaka University Medical School, Suita, Japan
    J Hum Genet 43:143-5. 1998
    We screened for germline mutations of mismatch repair genes, hMLH1 and hMSH2, in five Japanese families carrying hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with multiple primary cancers...
  84. pmc Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls
    S M Farrington
    Department of Surgery, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
    Am J Hum Genet 63:749-59. 1998
    ..We cloned and sequenced hMSH2 and hMLH1 introns, to optimize genomic sequencing...
  85. pmc Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer
    S Guerrette
    Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Cell Biol 18:6616-23. 1998
    ..human mismatch repair protein hMSH2 have been found to cosegregate with hereditary nonpolyposis colorectal cancer (HNPCC)...
  86. ncbi MSH2 genomic deletions are a frequent cause of HNPCC
    J Wijnen
    Nat Genet 20:326-8. 1998
  87. ncbi MSH2 codon 322 Gly to Asp seems not to confer an increased risk for colorectal cancer susceptibility
    T Liu
    Eur J Cancer 34:1981. 1998
  88. pmc BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures
    Y Wang
    Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:927-39. 2000
    ..This complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM, BLM, and the RAD50-MRE11-NBS1 protein complex...
  89. ncbi Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis
    L J Rasmussen
    Department of Life Sciences and Chemistry, Roskilde University, DK 4000, Roskilde, Denmark
    Mutat Res 460:41-52. 2000
    ..to identify tissue-specific MMR-associated factors, we employed the yeast two-hybrid system, using the human hMSH2 as bait and a human fetal liver library as prey...
  90. pmc Population carrier frequency of hMSH2 and hMLH1 mutations
    M G Dunlop
    Colon Cancer Genetics Group, Division of Molecular and Clinical Medicine, MRC Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK
    Br J Cancer 83:1643-5. 2000
    ..The estimated carrier prevalence in the population aged 15-74 years is 1:3139 (95% Cl = 1:1247-1:7626) and these carriers are at high risk of colorectal and other cancers...
  91. ncbi Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing
    J P Terdiman
    Department of Medicine, University of California, San Francisco, San Francisco, California, USA
    Gastroenterology 120:21-30. 2001
    The optimal strategy for the detection of hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers remains uncertain...
  92. ncbi Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae
    A R Ellison
    BitTech, Inc, Westlake Village, CA 91361, USA
    Hum Mol Genet 10:1889-900. 2001
    ..inherited disease caused by defects in the process of DNA mismatch repair (MMR), and mutations in the hMLH1 or hMSH2 genes are responsible for the majority of HNPCC...
  93. ncbi Mutational analysis of promoters of mismatch repair genes hMSH2 and hMLH1 in hereditary nonpolyposis colorectal cancer and early onset colorectal cancer patients: identification of three novel germ-line mutations in promoter of the hMSH2 gene
    Ki Hyuk Shin
    Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110 744, Korea
    Cancer Res 62:38-42. 2002
    The human DNA mismatch repair genes hMSH2 and hMLH1 are responsible for the development of hereditary nonpolyposis colorectal cancer (HNPCC)...
  94. ncbi Prevalence of germline mutations of MLH1 and MSH2 in hereditary nonpolyposis colorectal cancer families from Spain
    Trinidad Caldes
    Laboratory of Molecular Oncology, San Carlos University Hospital, Madrid, Spain
    Int J Cancer 98:774-9. 2002
    b>HNPCC is an autosomal dominantly inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and endometrial cancer at a young age...
  95. ncbi hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer
    Benedito Mauro Rossi
    Department of Pelvic Surgery, the Hospital do Câncer A C Camargo, Fundacao Antonio Prudente, Sao Paulo, Brazil
    Ann Surg Oncol 9:555-61. 2002
    The aim of this study was to search for mutations in the human mutS homolog 2 (hMSH2) and human mutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC).
  96. ncbi Hereditary nonpolyposis colorectal cancer: frequent occurrence of large genomic deletions in MSH2 and MLH1 genes
    Yaping Wang
    Institute of Human Genetics, University Clinics Bonn, Germany
    Int J Cancer 103:636-41. 2003
    Hereditary nonpolyposis colorectal cancer (HNPCC) is often caused by a deficiency in DNA mismatch repair...
  97. ncbi MSH2-deficient human cells exhibit a defect in the accurate termination of homology-directed repair of DNA double-strand breaks
    Josée France Villemure
    Department of Biochemistry, Universite de Montreal, Succ Centre Ville, Montreal, Quebec, Canada H3C 3J7
    Cancer Res 63:3334-9. 2003
    Mutations in the mismatch repair (MMR) genes hMSH2 and hMLH1 have been associated with hereditary nonpolyposis colorectal cancer...
  98. ncbi An intron splice acceptor polymorphism in hMSH2 and risk of leukemia after treatment with chemotherapeutic alkylating agents
    Lisa J Worrillow
    Leukaemia Research Fund Epidemiology and Genetics Unit, Academic Unit of Epidemiology, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom
    Clin Cancer Res 9:3012-20. 2003
    We sought to determine whether the -6 exon 13 T>C polymorphism in the DNA mismatch repair gene hMSH2 modulates susceptibility to acute myeloid leukemia after therapy and particularly after O(6)-guanine alkylating chemotherapy...
  99. pmc Missense mutations in hMLH1 and hMSH2 are associated with exonic splicing enhancers
    Ivan P Gorlov
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Am J Hum Genet 73:1157-61. 2003
    ..missense mutations (found in affected individuals) with high-score ESE motifs in the human mismatch-repair genes hMSH2 and hMLH1...
  100. ncbi Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden
    Kristina Cederquist
    Unit of Medical and Clinical Genetics, Department of Medical Biosciences, Umea University, Sweden
    Int J Cancer 109:370-6. 2004
    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder that predisposes to predominantly colorectal and endometrial cancers due to germline mutations in DNA mismatch repair genes, mainly MLH1, MSH2 and in ..
  101. ncbi Degadration of mismatch repair hMutSalpha heterodimer by the ubiquitin-proteasome pathway
    Hélène Hernandez-Pigeon
    INSERM U563, Centre de Physiopathologie Toulouse Purpan, Institut Claudius Regaud, 20 rue du Pont Saint Pierre, 31052 Toulouse, France
    FEBS Lett 562:40-4. 2004
    Mismatch repair plays a critical role in genome stability. This process requires several proteins including hMSH2/hMSH6 (hMutSalpha) heterodimer involved in the first stage of the process, the mispair recognition...

Research Grants62

  1. INHIBITION OF SPONTANEOUS MUTATION IN MISMATCH MUTATORS
    Catherine Klein; Fiscal Year: 2002
    ..Defects in mismatch repair have been identified in patients with hereditary non-polyposis colorectal cancer (HNPCC, Lynch Syndrome II), a condition characterized by an increased spontaneous mutation rate and a high degree of ..
  2. INHERITED MSH6 MUTATIONS IN DIVERSE COLORECTAL CANCERS
    Sapna Syngal; Fiscal Year: 2004
    ..MLH1, PMS1 and PMS2) have been identified primarily in families with hereditary nonpolyposis colorectal cancer (HNPCC) featuring high penetrance, early age at diagnosis, and right colon predominance...
  3. The Microsatellite Instability Phenotype
    MICHAEL SICILIANO; Fiscal Year: 2007
    DESCRIPTION (provided by applicant): Hereditary non-polyposis colon cancer (HNPCC) is a cancer syndrome shown to be the result of a mutator effect - inheritance of gene or genes with mutations detracting from the cells' ability to ..
  4. Screening Pretest for HNPCC
    Jeremy Fields; Fiscal Year: 2007
    ..for Phase II is to develop an immunoassay to diagnose individuals carrying a hereditary nonpolyposis colon cancer (HNPCC) trait. There are >2...
  5. NEW HUMAN DNA REPAIR ENDONUCLEASE
    Alfonso Bellacosa; Fiscal Year: 2002
    ..Patients with Hereditary Non-Polyposis Colorectal Cancer (HNPCC) carry a germline mutation in genes involved in DNA mismatch repair (h MSH2, h MLH1, GTBP /hMSH6, hPMS2 and hPMS1)...
  6. Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention
    Roberd Bostick; Fiscal Year: 2009
    ..have been found to be altered early in the two major colorectal carcinogenesis pathways (APC, -catenin, E-cadherin, MSH2), 2) cell cycle events in colorectal epithelial crypt cells (proliferation: Mib-1;differentiation: p21; apoptosis ..
  7. Sapna Syngal; Fiscal Year: 2016
    ..to be used by healthcare providers to estimate the probability that an individual carries a mutation in the MLH1, MSH2 and MSH6 mismatch repair (MMR) genes (Balmana et al. JAMA 2006, Kastrinos et. al Gastroenterology 2011)...
  8. MOLECULAR GENETIC ALTERATIONS OF ENDOMETRIAL CARCINOMA
    LORA ELLENSON; Fiscal Year: 1999
    ..frequent K-ras and p53 gene mutations, histopathological appearance, and occurrence in a familial cancer syndrome, HNPCC (hereditary non-polyposis colorectal cancer)...
  9. Gary M Kupfer; Fiscal Year: 2014
    ..research is that FANCD2 acts as a signal transduction protein to interact with downstream effectors such as the MSH2, the mismatch repair protein, and the MCM2-7 complex, which is critical for pre-origin loading of the replication ..
  10. ERIC E ALANI; Fiscal Year: 2016
    ..significant increases (~1000X) in mutation rate and have been implicated in hereditary forms of colon cancer (HNPCC)...
  11. The Familial Colorectal Neoplasia Collaborative Group
    STEPHEN NORMAN THIBODEAU; Fiscal Year: 2011
    ..molecular characterization core by continuing tumor phenotyping, performing germline mutation analysis on MLH1, MSH2, and MSH6 for the entire C-CFR, and dispatching products to other CFR sites for characterization of somatic MLH1 ..
  12. Repair of Oxidatively Damaged Guanines
    A LIEN L LU-CHANG; Fiscal Year: 2013
    ..In this context, the 9-1-1 proteins interact with and increase the activities DNA glycosylases and hMSH2/hMSH6 mismatch recognition complex...
  13. Mechanistic studies of DNA repair and damage response
    Dorothy A Erie; Fiscal Year: 2010
    ..The MutS homolog MSH2-MSH6 (MutS) binds preferentially to a DNA lesion and subsequently interacts with the MutL homolog MLH1-PMS2 (MLH1-..
  14. Mismatch Repair Functions Affected During Tumorigenesis
    Christopher D Heinen; Fiscal Year: 2012
    ..We will test this prediction by determining whether cancer-associated missense mutations of the MMR genes hMSH2 and hMSH6 affect both DNA repair and checkpoint/apoptosis response...
  15. Zhong Yun; Fiscal Year: 2014
    ..repression of several key DNA repair factors, including the DNA mismatch repair (MMR) factors, MLH1 and MSH2, and the homology-dependent repair (HDR) factors, RAD51 and BRCA1...
  16. Dorothy A Erie; Fiscal Year: 2016
    ..humans, mutations in the MutS and MutL homologs are directly linked to hereditary non-polyposis colorectal cancer (HNPCC) and are associated with sporadic cancers...
  17. Peter M Glazer; Fiscal Year: 2016
    ..stress causes decreased expression at the transcriptional level of the DNA mismatch repair (MMR) factors, MLH1 and MSH2, and of the homology- dependent repair (HDR) factors, RAD51 and BRCA1...
  18. PCNA clamp mechanisms in DNA replication and repair
    Manju M Hingorani; Fiscal Year: 2010
    ..With respect to a PCNA target, we plan to investigate the mechanism of action of S. cerevisiae Msh2-Msh6, an essential DNA mismatch repair protein that detects base pair errors in DNA and initiates repair in a an ..
  19. Roles for Mismatch Repair Proteins in Maintaining Genome Stability
    JENNIFER ANNE SURTEES; Fiscal Year: 2013
    ..We are particularly interested in the MSH2-MSH3 complex, which recognizes insertion/deletion loops as well as intermediates of genetic recombination...
  20. DNA repair mechanisms in trinucleotide repeat instability
    Guo Min Li; Fiscal Year: 2013
    ..Surprisingly, previous studies in transgenic mice suggest that mismatch recognition protein MSH2- MSH3 heterodimer (also called MutS2) promotes (CAG)n expansions by binding to (CAG)n-formed hairpins and ..
  21. Polly A Newcomb; Fiscal Year: 2014
    ..Participants have: (i) been tested for mutations in the mismatch repair genes (MLH1, MSH2, MSH6 and PMS2) and MUTYH, and measured for the single nucleotide polymorphisms (SNPs) known to be associated with ..
  22. Genetics/microsatellite instability in tumor suppressors
    Hanlee Ji; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Hereditary nonpolyposis colorectal cancer (HNPCC; OMIM 120435-6) is an autosomal dominant inherited syndrome caused by germline mutations in DNA mismatch repair (MMR) genes such as hMSH2 ..
  23. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2016
    ..The most prominent high-risk colorectal cancer susceptibility genes, APC, MLH1, MSH2, MSH6, PMS2, and PTEN, were all discovered more than a decade ago...
  24. Role of Kruppel-Like Factor 4 in Wnt and Notch Signaling in the Intestinal Tract
    Amr Ghaleb; Fiscal Year: 2010
    ..mutations in adenomatous polyposis coli (APC), p53, and genes involved in DMA mismatch repair such as MLH1 and MSH2, and oncogenic activation of KRAS and BRAF are important in the development of CRC...
  25. Escherichia coli and Colorectal Carcinogenesis
    Michael S Donnenberg; Fiscal Year: 2010
    ..coli (AEEC) strains specifically down-regulate expression of mismatch repair (MMR) proteins MLH1 and MSH2. These proteins protect against mutations during DNA replication and patients with certain inherited and some with ..
  26. Molecular Genetics of Colorectal Cancer Progression in a Diverse Patient Cohort
    BROOKE E SYLVESTER; Fiscal Year: 2011
    ..MLH1, MSH2, MSH6 and PMS2 are proteins expressed by mismatch repair genes that are responsible for repairing nucleotide ..
  27. XIAOHONG MARY ZHANG; Fiscal Year: 2016
    ..HDAC6, acts as both a deacetylase and a ubiquitin E3 ligase to promote a key DNA mismatch repair (MMR) protein MSH2 deacetylation, polyubiquitination and degradation...
  28. The Colon Cancer Family Registry: Hawaii
    Loic Le Marchand; Fiscal Year: 2011
    ..and immunohistochemistry (IHC) for DNA mismatch repair (MMR) defect and testing for germ-line mutations in MLH1, MSH2, MSH6 and MYH for PHASE I samples...
  29. Function of the AID C terminus in Ig class switching
    JANET M STAVNEZER; Fiscal Year: 2013
    ..regions cooperatively with other enzymes involved in introducing DNA breaks into S regions, specifically UNG and Msh2-Msh6, and that this binding is dependent upon the AID C terminus...
  30. The Colon Cancer Family Registry: Seattle
    Polly A Newcomb; Fiscal Year: 2011
    ..Core activities by submitting participant biospecimen samples for: screening for expression of MLH1, MSH2, and MSH6 proteins;MMR-mutation testing guided by the IHC results;MLH1 methylation testing;screening for selected ..
  31. Winfried Edelmann; Fiscal Year: 2016
    ..Mutations in mammalian MMR genes are causative in hereditary non-polyposis colorectal cancer /Lynch syndrome (HNPCC/LS) and many sporadic cancers...
  32. Identifying Conserved Genetic Networks for Eukaryotic MMR Genes
    Winfried Edelmann; Fiscal Year: 2012
    ..the focus of intensive research efforts because mutations in MMR genes are the underlying cause of Lynch syndrome (HNPCC, hereditary nonpolyposis colorectal cancer) and a significant proportion of sporadic colorectal cancers...
  33. The Colon Cancer Family Registry: USC Consortium
    ROBERT WILLIAM HAILE; Fiscal Year: 2011
    ..updates on family history of cancer and vital status, pathology reports and tumor blocks on any new CRC cases and HNPCC-related cancers, and informed consents for possible future studies of clinical data...
  34. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2016
    ..colorectal cancer syndrome, is caused by germline mutations in one of four DNA mismatch repair (MMR) genes- MLH1, MSH2, MSH6, and PMS2...
  35. IMMUNITY IN TRANSGENIC MICE
    Erik Selsing; Fiscal Year: 2010
    ..In mice lacking the DNA mismatch repair protein, Msh2, we have also found that the S? tandem repeats are critical for switching, indicating that different DNA regions ..
  36. Fay Kastrinos; Fiscal Year: 2014
    ..for Lynch Syndrome: MMRpredict, MMRpro, and PREMM1,2,6 (prediction of mismatch repair gene mutations in MLH1, MSH2, and MSH6)...
  37. Ajay Goel; Fiscal Year: 2016
    ..We will also look for evidence of methylation-induced silencing of the MSH2 and MSH6 genes, which also have CpG islands in their promoters, and should be susceptible to the same perturbation...
  38. Shizhen Emily Wang; Fiscal Year: 2016
    ..cancer cells, TGF- [unreadable] induces microRNAs (miR-21 and miR-181) that target the DNA damage sensors ATM and MSH2, and may therefore regulate cancer response to genotoxic chemotherapy...
  39. Richard Fishel; Fiscal Year: 2016
    ..provided by applicant): Defects in the core human mismatch repair (MMR) genes are the cause of Lynch syndrome (LS/HNPCC), as well as 10-40% of sporadic colorectal, gastric, endometrial, ovarian and upper urinary tract tumors...
  40. MULTIPLE RISKS, DECISIONS & BEHAVIORS IN THE GENOMIC ERA
    Karen E Hurley; Fiscal Year: 2010
    ..longitudinal patterns of adherence (full, partial or none) to comprehensive, multi-organ screening guidelines in HNPCC patients. Cluster analysis will yield a taxonomy of perceived/risk worry types (e.g...
  41. Annual Uterine Cancer Biology Symposium
    KAREN HSIEH contact LU; Fiscal Year: 2010
    ..in the management of advanced uterine cancer, a consensus conference on endometrial cancer and Lynch syndrome (HNPCC), integrating molecular biomarkers into clinical trials, and obesity and endometrial cancer...
  42. Genetic Testing and Cancer Screening in Hereditary Cancer Syndromes
    Elena Martinez Stoffel; Fiscal Year: 2011
    ..A cross-sectional questionnaire study of 400 individuals with Hereditary Nonpolyposis Colorectal Cancer (HNPCC) will provide baseline data on cancer prevention behaviors and will identify clinical characteristics associated ..
  43. KATRINA A GODDARD; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): Screening tests for Hereditary Non-Polyposis Colorectal Cancer (HNPCC) [also called Lynch Syndrome], are among the few available validated genetic tests that have been recommended as an evidence-..
  44. Molecular Characterization of Sporadic Colorectal Cancer in the Young from India
    Jonathan R Pollack; Fiscal Year: 2010
    ..the Hereditary Non-polyposis Colorectal Cancer (HNPCC) caused mainly due to germline inactivation of mismatch repair genes and the Familial Adenomatous Polyposis (FAP) ..
  45. Steven M Lipkin; Fiscal Year: 2014
    ..These complexes interact with MSH2/MSH6 and MSH2/MSH6 heterodimers...
  46. MOUSE MODELS FOR HUMAN CANCER
    Raju S Kucherlapati; Fiscal Year: 2013
    ..genes MLH1 and MSH2 result in a cancer predisposition syndrome, termed hereditary non-polyposis colorectal cancer (HNPCC). Mismatch repair (MMR) deficiency is also observed in a large number of sporadic tumors in different tissues...
  47. Incorporating genomics into routine clinical care for Veterans with colon cancer
    Sara J Knight; Fiscal Year: 2013
    ..to serve the nation at the forefront of genomic medicine and has selected hereditary nonpolyposis colon cancer (HNPCC) as the initial focus for clinical trials, there is little information available on the delivery of genomic ..
  48. Targeting the MSH2-dependent Apoptotic Pathway
    Freddie R Salsbury; Fiscal Year: 2013
    ..We are targeting a specific protein, the MMR protein MSH2 (MutS homolog 2), since we have shown that this protein undergoes specific conformational changes in response to ..
  49. Multiscale modeling of supramolecular protein-DNA assemblies
    Michael Feig; Fiscal Year: 2013
    ..Applications focus on DNA mismatch recognition and initiation of repair by bacterial MutS and eukaryotic MSH2-MSH6 as well as transcription by yeast RNA polymerase II...
  50. Mechanism of PCNA-dependent 5'->3' Mismatch Excision
    Guo Min Li; Fiscal Year: 2010
    ..genomic instability and eventually to cancer predisposition, including hereditary non-polyposis colorectal cancer (HNPCC) and certain types of sporadic cancers...
  51. Calcium, Vitamin D, and Markers of Adenomatous Polyps
    Roberd Bostick; Fiscal Year: 2006
    ..have been found to be altered early in the 2 major colorectal carcinogenesis pathways (ARC, B-catenin, E-cadherin, MSH2, MLH1), 3) a more complete picture of the cell cycle events in colorectal epithelial crypt cells (short and long-..
  52. Mechanisms of genomic instability in cancer
    Paul Watt; Fiscal Year: 2002
    ..Examples of such mutator genes are the mismatch repair genes such as MSH2 which are frequently mutated in HNPCC. Less work has focussed on identifying the key players responsible for abnormal recombination and missegregation ..
  53. Prophylactic colectomy intentions in HNPCC patients
    Karen Hurley; Fiscal Year: 2005
    Hereditary non-polyposis colorectal cancer (HNPCC) is associated with up to an 80 percent lifetime risk of developing colorectal cancer and a 40 to 50 percent chance of a metachronous tumor after partial colectomy for the disease...
  54. DNA MISMATCH REPAIR IN EUKARYOTES
    Satya Prakash; Fiscal Year: 2003
    ..instability, and mutations in human mismatch repair genes result in hereditary non-polyposis colorectal cancer (HNPCC) and other types of cancers...
  55. RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCER
    Walter Curran; Fiscal Year: 2004
    ..and families with familial adenomatous polyposis (FAP) and with hereditary non-polyposis colorectal cancer (HNPCC). However, the majority of colorectal cancer cases appear sporadic...
  56. Cell Cycle Control of Trinucleotide Instability in Mammalian Cells
    Irina V Kovtun; Fiscal Year: 2010
    ..Both events require the presence of mismatch repair enzyme Msh2. We and others have demonstrated that Msh2- dependent expansion in germ and somatic cells arises from repair at a ..
  57. CANCER SCREENING COMPLIANCE IN HEREDITARY COLON CANCER
    Sapna Syngal; Fiscal Year: 2005
    ..Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of hereditary colon cancer...
  58. AP4 Center for Studies on Hereditary Colorectal Cancer
    Bruce Boman; Fiscal Year: 2004
    ..will focus on hereditary colorectal cancer (HCC) because: I) HCC, including Hereditary Non-polyposis Colon Cancer (HNPCC) and Familial Adenomatous Polyposis (FAP) are subsets (approximately 3%, approximately 1%) of colorectal cancer (..
  59. MISMATCH REPAIR DEFECTS AND HUMAN TUMOR RADIOSENSITIZATI
    Timothy Kinsella; Fiscal Year: 2003
    ..cancers, along with the causal relationship previously observed with hereditary nonpolyposis colorectal cancers (HNPCC)...
  60. PHENOTYPIC AND PSYCHOSOCIAL STUDY OF THE L1307K MUTATION
    Henry Lynch; Fiscal Year: 2004
    ....
  61. Identification of Anticancer Drug Targets
    Robert Wilson; Fiscal Year: 2004
    ..genes that bring about synthetic lethality represent potential drug targets for cancers with mutations in hBUB1 or hMSH2. The Specific Aims are: 1) To identify genes by synthetic lethal analysis that are required for the viability of S...
  62. CELL CYCLE REGULATION BY THE MISMATCH REPAIR GENES
    John Carethers; Fiscal Year: 1999
    ..We will examine two of the mismatch repair genes, hMLH1 and hMSH2, to determine if there are differences in specificity of cell cycle regulation between the two genes...