MLH1

Summary

Gene Symbol: MLH1
Description: mutL homolog 1
Alias: COCA2, FCC2, HNPCC, HNPCC2, hMLH1, DNA mismatch repair protein Mlh1, mutL homolog 1, colon cancer, nonpolyposis type 2
Species: human

Top Publications

  1. ncbi Evidence for heritable predisposition to epigenetic silencing of MLH1
    Huiping Chen
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Int J Cancer 120:1684-8. 2007
  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. ncbi Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes
    V Pensotti
    Division of Experimental Oncology A, Istituto Nazionale Tumori, Milano, Italy
    Genes Chromosomes Cancer 19:135-42. 1997
  4. ncbi Polymorphisms in hMLH1 and risk of early-onset lung cancer in a southeast Chinese population
    Yu An
    State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Handan Road, Shanghai 200433, China
    Lung Cancer 59:164-70. 2008
  5. ncbi Racial differences in MLH1 and MSH2 mutation: an analysis of yellow race and white race based on the InSiGHT database
    Wenqian Wei
    Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University, Shanghai, P R China
    J Bioinform Comput Biol 8:111-25. 2010
  6. doi The association between MLH1 -93 G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis
    Xin min Pan
    Department of Forensic Pathology, College of Forensic Medicine, Henan University of Science and Technology, 31 Anhui Road, Jianxi District, Luoyang, Henan 471003, People s Republic of China
    Mutagenesis 26:667-73. 2011
  7. 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
  8. pmc Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening
    Jenny N Poynter
    Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033 9176, USA
    Cancer Epidemiol Biomarkers Prev 17:3208-15. 2008
  9. ncbi Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer
    C E Bronner
    Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201 3098
    Nature 368:258-61. 1994
  10. ncbi MLH1 -93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancer
    Stavroula Raptis
    Department of Pathology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5T 3L9
    J Natl Cancer Inst 99:463-74. 2007

Research Grants

  1. INHIBITION OF SPONTANEOUS MUTATION IN MISMATCH MUTATORS
    Catherine Klein; Fiscal Year: 2002
  2. Dorothy A Erie; Fiscal Year: 2016
  3. NEW HUMAN DNA REPAIR ENDONUCLEASE
    Alfonso Bellacosa; Fiscal Year: 2002
  4. NORALANE MOREY LINDOR; Fiscal Year: 2016
  5. Michael Wargovich; Fiscal Year: 2014
  6. MOLECULAR GENETIC ALTERATIONS OF ENDOMETRIAL CARCINOMA
    LORA ELLENSON; Fiscal Year: 1999
  7. Gary M Kupfer; Fiscal Year: 2014
  8. ERIC E ALANI; Fiscal Year: 2016
  9. Mechanistic studies of DNA repair and damage response
    Dorothy A Erie; Fiscal Year: 2010
  10. Mismatch Repair Functions Affected During Tumorigenesis
    Christopher D Heinen; Fiscal Year: 2012

Detail Information

Publications325 found, 100 shown here

  1. ncbi Evidence for heritable predisposition to epigenetic silencing of MLH1
    Huiping Chen
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Int J Cancer 120:1684-8. 2007
    Epigenetic silencing of MLH1 is the most common cause of defective DNA mismatch repair in endometrial and colorectal cancers...
  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. ncbi Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes
    V Pensotti
    Division of Experimental Oncology A, Istituto Nazionale Tumori, Milano, Italy
    Genes Chromosomes Cancer 19:135-42. 1997
    Fourteen Italian families affected with hereditary nonpolyposis colorectal cancer (HNPCC) were screened for germline mutations at three DNA mismatch repair (MMR) genes, MSH2, MLHI, and GTBP, by using a combination of different methods ..
  4. ncbi Polymorphisms in hMLH1 and risk of early-onset lung cancer in a southeast Chinese population
    Yu An
    State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Handan Road, Shanghai 200433, China
    Lung Cancer 59:164-70. 2008
    ..Defects in MMR genes have been involved in several types of sporadic and hereditary cancers. hMLH1 is considered one of central members of the MMR pathway...
  5. ncbi Racial differences in MLH1 and MSH2 mutation: an analysis of yellow race and white race based on the InSiGHT database
    Wenqian Wei
    Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University, Shanghai, P R China
    J Bioinform Comput Biol 8:111-25. 2010
    MLH1 and MSH2 mutations underlie 90% of hereditary nonpolyposis colorectal cancer (HNPCC) mutations...
  6. doi The association between MLH1 -93 G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis
    Xin min Pan
    Department of Forensic Pathology, College of Forensic Medicine, Henan University of Science and Technology, 31 Anhui Road, Jianxi District, Luoyang, Henan 471003, People s Republic of China
    Mutagenesis 26:667-73. 2011
    ..Polymorphisms of MLH1 in individuals may have an effect on the DNA repair capacity and therefore on cancer risk...
  7. 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...
  8. pmc Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening
    Jenny N Poynter
    Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033 9176, USA
    Cancer Epidemiol Biomarkers Prev 17:3208-15. 2008
    Microsatellite instability (MSI) occurs in 10% to 20% of colorectal cancers (CRC) and has been attributed to both MLH1 promoter hypermethylation and germline mutation in the mismatch repair (MMR) genes...
  9. ncbi Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer
    C E Bronner
    Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201 3098
    Nature 368:258-61. 1994
    ..3). Here we report that a human gene encoding a protein, hMLH1 (human MutL homologue), homologous to the bacterial DNA mismatch repair protein MutL, is located on human ..
  10. ncbi MLH1 -93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancer
    Stavroula Raptis
    Department of Pathology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5T 3L9
    J Natl Cancer Inst 99:463-74. 2007
    ..We investigated whether polymorphisms in DNA mismatch repair genes are associated with the risk of colorectal cancer...
  11. doi Multiplex SNaPshot genotyping for detecting loss of heterozygosity in the mismatch-repair genes MLH1 and MSH2 in microsatellite-unstable tumors
    Maria Bujalkova
    Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Bratislava, Slovakia
    Clin Chem 54:1844-54. 2008
    In the workup of patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC), detection of loss of heterozygosity (LOH) could help pinpoint the mismatch-repair (MMR) gene carrying the germline mutation, but analysis of ..
  12. ncbi Mutation of a mutL homolog in hereditary colon cancer
    N Papadopoulos
    Johns Hopkins Oncology Center, Baltimore, MD 21231
    Science 263:1625-9. 1994
    ..One of these genes (hMLH1) resides on chromosome 3p21, within 1 centimorgan of markers previously linked to cancer susceptibility in HNPCC ..
  13. ncbi -93G-->A polymorphism of hMLH1 and risk of primary lung cancer
    Sun Ha Park
    Cancer Research Institute, Kyungpook National University Hospital, Daegu, South Korea
    Int J Cancer 112:678-82. 2004
    ..We investigated the association between the -93G-->A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population...
  14. doi Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population
    Mef Nilbert
    Clinical Research Centre and HNPCC Register, Copenhagen University, Hvidovre University Hospital, Kettegard Alle 30, Hvidovre, 2650, Denmark
    Fam Cancer 8:75-83. 2009
    ..number of mismatch-repair (MMR) gene mutations have been identified in hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome...
  15. 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
    ..predisposition to cancer that has recently been linked to defects in the human mismatch repair genes hMSH2 and hMLH1. The identification of the causative mutations in HNPCC families is desirable, since it confirms the diagnosis and ..
  16. 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...
  17. 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
  18. 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-H) phenotype, frequently identified in hereditary nonpolyposis colorectal cancer (HNPCC), also accounts for approximately 15% of sporadic colorectal cancers...
  19. 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.
  20. pmc Two novel germline mutations of MLH1 and investigation of their pathobiology in hereditary non-polyposis colorectal cancer families in China
    Chao Fu Wang
    Department of Pathology, Cancer Hospital of Fudan University, 270 DongAn Road, Shanghai 200032, China
    World J Gastroenterol 13:6254-8. 2007
    ..microsatellite instability and expression of MLH1 in tumor tissues of hereditary non-polyposis colorectal cancer (HNPCC) with two novel germline mutations, and further investigate the pathobiology of the two novel mutations of MLH1.
  21. doi Estrogen stimulates the expression of mismatch repair gene hMLH1 in colonic epithelial cells
    Peng Jin
    Department of Gastroenterology, Beijing Military General Hospital, People s Republic of China
    Cancer Prev Res (Phila) 3:910-6. 2010
    ..In cultured COLO205 cells, the effect of estradiol (E2) and antagonist ICI182.780 on the expression of hMLH1 and hMSH2 was studied using reverse transcription-PCR and Western blotting...
  22. ncbi Alternative splicing of MLH1 messenger RNA in human normal cells
    F Charbonnier
    Laboratoire de Genetique Moleculaire, Centre Hospitalo Universitaire de Rouen, France
    Cancer Res 55:1839-41. 1995
    The hMLH1 protein, composed of 756 amino acids, is the human homologue of the bacterial DNA mismatch repair protein MutL, and germ line mutations of the hMLH1 gene have been identified in kindreds with hereditary nonpolyposis colorectal ..
  23. 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 ..
  24. 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...
  25. ncbi Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients
    Heather Hampel
    Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, 420 West 12th Avenue, Columbus, OH 43210, USA
    Cancer Res 66:7810-7. 2006
    ..Patients with MSI-positive tumors underwent testing for germ line mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21...
  26. ncbi Promoter hypermethylation is the predominant mechanism in hMLH1 and hMSH2 deregulation and is a poor prognostic factor in nonsmoking lung cancer
    Han Shui Hsu
    Division of Thoracic Surgery, Departments of Surgery and Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
    Clin Cancer Res 11:5410-6. 2005
    ..Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non-small cell lung cancer (NSCLC) patients...
  27. pmc Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients
    Andrea Mann
    CR UK Genetic Epidemiology Unit, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
    Eur J Cancer 44:2259-65. 2008
    ..The aim of this study was to investigate the possible association between the common variants in MMR genes and invasive ovarian cancer overall survival...
  28. ncbi Founding mutations and Alu-mediated recombination in hereditary colon cancer
    M Nystrom-Lahti
    Department of Medical Genetics, University of Helsinki, Finland
    Nat Med 1:1203-6. 1995
    By screening members of Finnish families displaying hereditary nonpolyposis colorectal cancer (HNPCC) for predisposing germline mutations in MSH2 and MLH1, we show that two mutations in MLH1 together account for 63% (19/30) of kindreds ..
  29. ncbi Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis
    C Ban
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 95:541-52. 1998
    ..We provide evidence that the flexible, yet conserved, loops surrounding this ATP-binding site undergo conformational changes upon ATP hydrolysis thereby modulating interactions between MutL and other components of the repair machinery...
  30. ncbi The interaction of the human MutL homologues in hereditary nonpolyposis colon cancer
    S Guerrette
    Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 274:6336-41. 1999
    ..for approximately 70% of the common cancer susceptibility syndrome hereditary nonpolyposis colorectal cancer (HNPCC)...
  31. ncbi Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system
    Joerg Trojan
    Second Department of Medicine, Johann Wolfgang Goethe University, Frankfurt a M, Germany
    Gastroenterology 122:211-9. 2002
    Germline mutations in the DNA mismatch repair (MMR) genes hMLH1 and hMSH2 are associated with susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC)...
  32. 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).
  33. ncbi MSI in endometrial carcinoma: absence of MLH1 promoter methylation is associated with increased familial risk for cancers
    Alison J Whelan
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA
    Int J Cancer 99:697-704. 2002
    ..feature of colorectal and endometrial tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC). Sporadic colorectal and endometrial cancers that exhibit MSI frequently have methylation of the MLH1 promoter...
  34. ncbi BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes
    Enric Domingo
    Molecular Oncology and Aging Research, Centre d Investigacions en Bioquimica i Biologia Molecular CIBBIM, Hospital Universitari Vall d Hebron, Passeig Vall d Hebron 119 129, Barcelona 08035, Spain
    Oncogene 24:3995-8. 2005
    ..Moreover, BRAF mutations proved to be absent in tumors from hereditary nonpolyposis colorectal cancer syndrome (HNPCC) families with germline mutations in the MMR genes MLH1 and MSH2...
  35. ncbi Genomic rearrangements in MSH2 and MLH1 are rare mutational events in Spanish patients with hereditary nonpolyposis colorectal cancer
    Sergi Castellvi-Bel
    Gastroenterology Department, Institut de Malalties Digestives, IDIBAPS, Barcelona, Catalonia, Spain
    Cancer Lett 225:93-8. 2005
    ..Hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent autosomal dominant predisposition to the development of CRC, accounting for approximately 2...
  36. ncbi Analysis of the human MutLalpha.MutSalpha complex
    Guido Plotz
    University of the Saarland, Klinik fur Innere Medizin II, Homburg Saar, Germany
    Biochem Biophys Res Commun 340:852-9. 2006
    ..The described conditions likely capture an intermediate of the repair reaction which has bound ATP and ADP in the two nucleotide-binding sites of MutSalpha...
  37. 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)...
  38. ncbi Single-nucleotide polymorphisms of mismatch repair genes in healthy Chinese individuals and sporadic colorectal cancer patients
    Qian Mei
    Department of Medical Genetics, The Second Military Medical University, Xiangyin Road 800, Shanghai, China
    Cancer Genet Cytogenet 171:17-23. 2006
    ..Three SNPs (MLH1 394G-->C, 655A-->G, 1151T-->A) occurred with a frequency of 8.8-11.2% in the Chinese population...
  39. 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)...
  40. ncbi Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays
    Masanobu Takahashi
    Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University Hospital, Tohoku University, Sendai, Japan
    Cancer Res 67:4595-604. 2007
    ..We previously established an assay for detecting loss-of-function mutations in the MLH1 gene using a dominant mutator effect of human MLH1 expressed in Saccharomyces cerevisiae...
  41. 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 ..
  42. ncbi Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer
    Rebecca A Barnetson
    University of Edinburgh Cancer Research Centre, School of Molecular and Clinical Medicine and Medical Research Council MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom
    Hum Mutat 29:367-74. 2008
    ..Patient samples were screened for germline mutations in MLH1, MSH2, and MSH6...
  43. pmc The interplay between hMLH1 and hMRE11: role in MMR and the effect of hMLH1 mutations
    Nianxi Zhao
    School of Molecular Biosciences and Center for Reproductive Biology, P O Box 644660, Washington State University, Pullman, WA 99164 4660, USA
    Biochem Biophys Res Commun 370:338-43. 2008
    ..studies indicate that hMRE11 plays a role in MMR, and this function of hMRE11 is most likely mediated by the hMLH1-hMRE11 interaction...
  44. 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...
  45. pmc Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16
    J Wijnen
    MGC Department of Human Genetics, Medical Genetics Center, Sylvius Laboratory, Leiden University, The Netherlands
    Am J Hum Genet 58:300-7. 1996
    ..Inherited mutations in at least four DNA mismatch repair genes, hMSH2, hMLH1, hPMS1, and hPMS2, are known to cause HNPCC...
  46. ncbi Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer
    P Hutter
    DNA Laboratory, Pathology Division, ICHV, Sion, Switzerland
    Int J Cancer 78:680-4. 1998
    Lynch syndrome, or hereditary non-polyposis colorectal cancer (HNPCC), is a consequence of a dominantly inherited susceptibility to accumulate somatic mutations...
  47. 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...
  48. 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...
  49. ncbi Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer
    Minna Nystrom-Lahti
    Department of Biosciences, Division of Genetics, University of Helsinki, Helsinki, Finland
    Genes Chromosomes Cancer 33:160-7. 2002
    Hereditary nonpolyposis colon cancer (HNPCC) is associated with malfunction of postreplicative mismatch repair (MMR)...
  50. ncbi Mutation analysis of MLH1 and MSH2 genes performed by denaturing high-performance liquid chromatography
    Grzegorz Kurzawski
    Hereditary Cancer Center Department of Genetics and Pathology, Pomeranian Academy of Medicine, ul Polabska 4, 70 115, Szczecin, Poland
    J Biochem Biophys Methods 51:89-100. 2002
    ..Studies included a series of 46 patients affected by colorectal cancer from HNPCC families...
  51. 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...
  52. ncbi hMLH1 and hMSH2 somatic inactivation mechanisms in sporadic colorectal cancer patients
    Eniko Kamory
    Department of Pathogenetics, National Institute of Oncology, Budapest, H 1122, Hungary
    Pathol Oncol Res 9:236-41. 2003
    ..In hereditary cases the hMLH1 and hMSH2 genes were shown to have a great importance, and in order to examine the somatic inactivation mechanisms ..
  53. ncbi The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer
    Steven M Lipkin
    Division of Oncology, Department of Medicine, University of California, Irvine, Irvine, California 92697, USA
    Nat Genet 36:694-9. 2004
    ..MLH1, MSH2 and MSH6 mutations underlie high-penetrance CRC susceptibility in hereditary nonpolyposis colon cancer (HNPCC), we hypothesized that attenuated alleles might also underlie susceptibility to sporadic CRC...
  54. ncbi The profile of hMLH1 methylation and microsatellite instability in colorectal and non-small cell lung cancer
    Toshiyuki Okuda
    Department of Surgery, Kanazawa University School of Medicine, 13 1 Takaramachi, Kanazawa 920 8641, Japan
    Int J Mol Med 15:85-90. 2005
    Microsatellite instability (MSI) is caused mainly by dysfunction of hMLH1, where aberrant hypermethylation (HM) of its promoter region is involved...
  55. 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...
  56. ncbi The mechanism of microsatellite instability is different in synchronous and metachronous colorectal cancer
    Fernando S Velayos
    Division of Gastroenterology and Colorectal Cancer Prevention Center, Department of Medicine, University of California San Francisco, California, USA
    J Gastrointest Surg 9:329-35. 2005
    b>MLH1 promoter hypermethylation has been described as the primary mechanism for high-frequency microsatellite instability (MSI-H) in sporadic colorectal cancers (CRCs)...
  57. ncbi Molecular characterization of the spectrum of genomic deletions in the mismatch repair genes MSH2, MLH1, MSH6, and PMS2 responsible for hereditary nonpolyposis colorectal cancer (HNPCC)
    Heleen van der Klift
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Genes Chromosomes Cancer 44:123-38. 2005
    A systematic search by Southern blot analysis in a cohort of 439 hereditary nonpolyposis colorectal cancer (HNPCC) families for genomic rearrangements in the main mismatch repair (MMR) genes, namely, MSH2, MLH1, MSH6, and PMS2, ..
  58. ncbi Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk
    Kyoung Mu Lee
    Department of Preventive Medicine, Seoul National University College of Medicine, Chongno Gu, Seoul, Korea
    Clin Cancer Res 11:4620-6. 2005
    ..To evaluate the role of genetic polymorphisms of DNA repair genes in breast cancer, we conducted a hospital-based case-control study of Korean women...
  59. pmc Mutually exclusive promoter hypermethylation patterns of hMLH1 and O6-methylguanine DNA methyltransferase in colorectal cancer
    Edward J Fox
    Department of Pathology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    J Mol Diagn 8:68-75. 2006
    ..Promoter hypermethylation of hMLH1 has been implicated in a subset of colorectal cancers that show microsatellite instability (MSI)...
  60. 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.
  61. ncbi Germline mutations and polymorphic variants in MMR, E-cadherin and MYH genes associated with familial gastric cancer in Jiangsu of China
    Yuanying Zhang
    Department of Molecular Biology, Jiangsu Institute of Cancer Research, Nanjing, China
    Int J Cancer 119:2592-6. 2006
    Germline mutations in MSH2, MLH1, E-cadherin and MutY (MYH) genes have been implicated in the occurrence of gastric cancer (GC)...
  62. 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
    ..if MSI testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations...
  63. ncbi Distinction of hereditary nonpolyposis colorectal cancer and sporadic microsatellite-unstable colorectal cancer through quantification of MLH1 methylation by real-time PCR
    Marcus Bettstetter
    Institute of Pathology and Molecular Diagnostics, University of Regensburg, Regensburg, Germany
    Clin Cancer Res 13:3221-8. 2007
    ..MSI-H is also a hallmark of hereditary nonpolyposis colorectal cancer (HNPCC) in which mismatch repair inactivation results from germ-line mutations...
  64. pmc Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island
    Joy C Lin
    Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
    Cancer Cell 12:432-44. 2007
    ..Here, we show that silencing of the three transcription start sites in the bidirectional MLH1 promoter CpG island in cancer cells involves distinct changes in nucleosomal occupancy...
  65. pmc DLEC1 and MLH1 promoter methylation are associated with poor prognosis in non-small cell lung carcinoma
    T J Seng
    Cancer Research Program, Garvan Institute of Medical Research, Sydney 2010, Australia
    Br J Cancer 99:375-82. 2008
    ..This study set out to investigate promoter methylation in the deleted in lung and oesophageal cancer 1 (DLEC1), MLH1 and other 3p genes in 239 non-small cell lung carcinomas (NSCLC). DLEC1 was methylated in 38.7%, MLH1 in 35...
  66. doi Redundant DNA methylation in colorectal cancers of Lynch-syndrome patients
    Aster Alemayehu
    Cancer Research Institute of Slovak Academy of Sciences, Bratislava, Slovakia
    Genes Chromosomes Cancer 47:906-14. 2008
    ..The crucial cause is DNA mismatch repair (MMR) malfunction that is associated mostly with MLH1 or MSH2 germline mutations...
  67. doi Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United States
    Fay Kastrinos
    Division of Gastroenterology, Brigham and Women s Hospital, Boston, Massachusetts, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 17:2044-51. 2008
    Lynch syndrome is caused by germ-line mismatch repair gene mutations. We examined the phenotypic differences between MLH1 and MSH2 gene mutation carriers and whether mutation type (point versus large rearrangement) affected phenotypic ..
  68. doi Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer?
    E Tulupova
    Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Mutat Res 648:40-5. 2008
    ..34; 95% CI 1.03-1.74). The carriers of the variant allele for the polymorphism IVS9-1406C>T in hMLH1 exhibited a decreased risk of rectal cancer (OR 0.71; 95% CI 0.51-0.98)...
  69. doi Comparative in silico analyses and experimental validation of novel splice site and missense mutations in the genes MLH1 and MSH2
    Beate Betz
    Institut fuer Humangenetik, Universitaetsklinikum Duesseldorf, Universitaetsstrasse 1, 40225 Duesseldorf, Germany
    J Cancer Res Clin Oncol 136:123-34. 2010
    ..colorectal cancer and other malignancies, is caused by inactivating mutations of DNA mismatch repair genes, mainly MLH1 and MSH2...
  70. doi Germ-line mutations in mismatch repair genes associated with prostate cancer
    Eli Marie Grindedal
    Section for Inherited Cancer, Department of Medical Genetics, Rikshospitalet University Hospital, N 0310 Oslo, Norway
    Cancer Epidemiol Biomarkers Prev 18:2460-7. 2009
    ..The mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 are associated with Lynch syndrome where colon and endometrial cancers are the predominant ..
  71. pmc Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass
    J Xie
    Department of Cancer Biology, University of Massachusetts Medical School, Women s Cancers Program, UMASS Memorial Cancer Center, Worcester, MA 01605, USA
    Oncogene 29:2499-508. 2010
    ..the poleta-dependent bypass promoted by FANCJ requires the direct binding to the mismatch repair (MMR) protein, MLH1. Together, our findings implicate that in human cells BRCA1 binding to FANCJ is critical to regulate DNA repair ..
  72. pmc De novo constitutional MLH1 epimutations confer early-onset colorectal cancer in two new sporadic Lynch syndrome cases, with derivation of the epimutation on the paternal allele in one
    Ajay Goel
    Gastrointestinal Cancer Research Laboratory, Baylor University Medical Center, Dallas, TX, USA
    Int J Cancer 128:869-78. 2011
    ..dominant cancer predisposition syndrome classically caused by germline mutations of the mismatch repair genes, MLH1, MSH2, MSH6 and PMS2...
  73. doi Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt
    Thanaa E A Helal
    Department of Pathology, Ain Shams University, Cairo, Egypt
    APMIS 118:934-40. 2010
    ..All cases were examined immunohistochemically to demonstrate the protein expression of hMSH2 and hMLH1. Thirty-two (64%) and 35 (70%) of the HCC cases revealed reduced expression of hMSH2 and hMLH1, respectively...
  74. doi Functional effects of the MLH1-93G>A polymorphism on MLH1/EPM2AIP1 promoter activity
    Sheron Perera
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 1 King s College Circle, Toronto, ON, Canada
    Oncol Rep 25:809-15. 2011
    ..We previously showed that the MLH1-93G>A promoter polymorphism is strongly associated with MSI tumours, suggesting a modifier role for this ..
  75. doi Gene expression profile and mutational analysis of DNA mismatch repair genes in carcinoma prostate in Indian population
    Abha Soni
    Institute of Pathology, Indian Council of Medical Research, Tumour Biology, New Delhi, India
    OMICS 15:319-24. 2011
    ..Thus, the present study investigated the gene expression profile of six major MMR genes, viz. hMLH1, hMSH2, hPMS1, hPMS2, hMSH3, and hMSH6, and polymorphism in hMLH1 and hMSH2 in Pca in Indian population...
  76. 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
    ..with 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 ..
  77. ncbi MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies
    Jia Li Xu
    Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    Asian Pac J Cancer Prev 13:901-7. 2012
    Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk...
  78. ncbi Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations
    R D Kolodner
    Division of Cell and Molecular Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115
    Cancer Res 55:242-8. 1995
    ..susceptibility syndrome known to be caused by inheritance of mutations in at least four genes such as hMSH2, hMLH1, hPMS1, and hPMS2 which encode components of a DNA mismatch repair system...
  79. 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...
  80. ncbi Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC families
    Q Wang
    Laboratoire d Oncologie Moleculaire, Unité INSERM 453, Centre Leon Berard, Lyon, France
    Int J Cancer 73:831-6. 1997
    ..The majority of the HNPCC families carry germline mutations of either hMSH2 or hMLH1 genes, whereas germline mutations of hPMS1 and hPMS2 genes have rarely been observed...
  81. 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
    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal, dominantly inherited cancer-prone syndrome...
  82. 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...
  83. 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)...
  84. ncbi Contribution of human mlh1 and pms2 ATPase activities to DNA mismatch repair
    Guy Tomer
    Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Biol Chem 277:21801-9. 2002
    MutLalpha, a heterodimer composed of Mlh1 and Pms2, is the major MutL activity in mammalian DNA mismatch repair. Highly conserved motifs in the N termini of both subunits predict that the protein is an ATPase...
  85. ncbi Different molecular mechanisms underlie genomic deletions in the MLH1 Gene
    Alessandra Viel
    Divisione di Oncologia Sperimentale 1, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
    Hum Mutat 20:368-74. 2002
    In this study we examined a series of 52 patients belonging to hereditary nonpolyposis colorectal cancer (HNPCC) or HNPCC-related families, all who had previously tested negative for mismatch repair (MMR) gene point mutations...
  86. 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...
  87. pmc N-terminus of hMLH1 confers interaction of hMutLalpha and hMutLbeta with hMutSalpha
    Guido Plotz
    2nd Department of Medicine, University of the Saarland, Kirrberger Strasse, D 66421 Homburg Saar, Germany
    Nucleic Acids Res 31:3217-26. 2003
    ..In humans, the two protein heterodimers hMutSalpha (hMSH2-hMSH6) and hMutLalpha (hMLH1-hPMS2) constitute the centre of the repair reaction...
  88. ncbi Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis
    Maran J W Berends
    Department of Gynaecology, University Hospital Groningen, Hanzeplein 1, PO Box 30 001, 9700 RB Groningen, The Netherlands
    J Clin Oncol 21:4364-70. 2003
    ....
  89. ncbi Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA
    Finn Cilius Nielsen
    Department of Clinical Biochemistry, Rigshospitalet, DK 2100 Copenhagen, Denmark
    Oncogene 23:1457-68. 2004
    ..We also show that both hMLH1-hPMS2 (MutLalpha) and hMLH1-hEXO1 complexes are formed in a reaction mixture containing all three proteins...
  90. 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.
  91. pmc BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing
    E Domingo
    Centre d Investigacions en Bioquimica i Biologia Molecular CIBBIM, Hospital Universitari Vall d Hebron, Passeig Vall d Hebron 119 129, Barcelona 08035, Spain
    J Med Genet 41:664-8. 2004
    According to the international criteria for hereditary non-polyposis colorectal cancer (HNPCC) diagnostics, cancer patients with a family history or early onset of colorectal tumours showing high microsatellite instability (MSI-H) should ..
  92. ncbi Ten novel MSH2 and MLH1 germline mutations in families with HNPCC
    Stefan Kruger
    Department of Surgical Research, Universitatsklinikum Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
    Hum Mutat 24:351-2. 2004
    Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer-susceptibility syndromes. Germline mutations in mismatch repair genes are associated with the clinical phenotype of HNPCC...
  93. 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...
  94. 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...
  95. 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...
  96. 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...
  97. ncbi Assessment of MLH1 promoter methylation in relation to gene expression requires specific analysis
    E Capel
    INSERM, U762, Paris, France
    Oncogene 26:7596-600. 2007
    ..In most sporadic MSI cases, the DNA mismatch repair (MMR) defect is due to methylation of the MLH1 promoter. In hereditary MSI cases, it is the consequence of germline mutations of one of the MMR genes...
  98. pmc Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: implications for genetic testing
    Janos Papp
    Department Molecular Genetics, National Institute of Oncology, Rath Gy u 7 9, H 1122 Budapest, Hungary
    World J Gastroenterol 13:2727-32. 2007
    To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families.
  99. doi Further evidence for heritability of an epimutation in one of 12 cases with MLH1 promoter methylation in blood cells clinically displaying HNPCC
    Monika Morak
    Department of Internal Medicine, Campus Innenstadt, University Hospital of the Ludwig Maximilians University, Munich, Germany
    Eur J Hum Genet 16:804-11. 2008
    ..tumours with high microsatellite instability (MSI-H) and loss of MMR protein expression are the hallmarks of HNPCC (Lynch syndrome)...
  100. pmc Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factors
    P T Campbell
    Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4 B402, Seattle, WA 98109 1024, USA
    Gut 58:661-7. 2009
    ..Less understood is the risk of colon cancer associated with common polymorphisms in MMR genes and the potential interacting role of lifestyle factors known to damage DNA...
  101. doi MLH1 -93G>A promoter polymorphism and risk of mismatch repair deficient colorectal cancer
    James M Allan
    Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom
    Int J Cancer 123:2456-9. 2008
    Rare inherited mutations in the mutL homolog 1 (MLH1) DNA mismatch repair gene can confer an increased susceptibility to colorectal cancer (CRC) with high penetrance where disease frequently develops in the proximal colon...

Research Grants64

  1. INHIBITION OF SPONTANEOUS MUTATION IN MISMATCH MUTATORS
    Catherine Klein; Fiscal Year: 2002
    ..by lycopene, soybean products, and EGCG in two cell lines, each defective in one mismatch repair gene, hPMS2 or Hmlh1. Aim 3 will determine whether the same anti-carcinogens can also reduce the observed microsatellite instability ..
  2. 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...
  3. 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)...
  4. NORALANE MOREY LINDOR; Fiscal Year: 2016
    ..since baseline;(ii) sub typing incident colorectal cancer tumors by immunohistochemistry, BRAF, K-ras, and MLH1 promoter methylation;(iii) genotyping, where indicated, participants for known familial mutations in DNA mismatch ..
  5. Michael Wargovich; Fiscal Year: 2014
    ..if EGCG is responsible for changes in HDACs that associate with the promoter region of RXRa, RAR[unreadable], hMLH1, p14arf, and p16INK4a and compare this activity with other known inhibitors of HDACs...
  6. 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)...
  7. Gary M Kupfer; Fiscal Year: 2014
    ..Aim #2: Determine the functional consequence of FANCD2-MLH1 interaction The working hypothesis for Aim #2 is that FANCD2-MLH1 interaction is important for the normal DNA ..
  8. ERIC E ALANI; Fiscal Year: 2016
    ..significant increases (~1000X) in mutation rate and have been implicated in hereditary forms of colon cancer (HNPCC)...
  9. Mechanistic studies of DNA repair and damage response
    Dorothy A Erie; Fiscal Year: 2010
    ..MutS homolog MSH2-MSH6 (MutS) binds preferentially to a DNA lesion and subsequently interacts with the MutL homolog MLH1-PMS2 (MLH1-PMS1 in yeast;MutL), but instead of initiating DNA mismatch repair, these interactions activate cell-..
  10. Mismatch Repair Functions Affected During Tumorigenesis
    Christopher D Heinen; Fiscal Year: 2012
    ..The most common disease predisposing patients to colorectal cancer is hereditary non-polyposis colon cancer (HNPCC) which stems from mutations in DNA mismatch repair (MMR) genes...
  11. Zhong Yun; Fiscal Year: 2014
    ..to transcriptional 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...
  12. Peter M Glazer; Fiscal Year: 2016
    ..hypoxic 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...
  13. 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)...
  14. Genetics/microsatellite instability in tumor suppressors
    Hanlee Ji; Fiscal Year: 2007
    ..dominant inherited syndrome caused by germline mutations in DNA mismatch repair (MMR) genes such as hMSH2 and hMLH1. With the loss of both alleles, DNA mismatch repair activity is completely lost and mutation rates increase ..
  15. 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...
  16. METHYLMAP: A TECHNOLOGY TO ANALYZE PROMOTER METHYLATION IN MICRODISSECTED CELLS
    Robi D Mitra; Fiscal Year: 2011
    ..1) multiplexed amplification of 90 loci from a single sample, 2) deep single molecule bisulfite sequencing of the MLH1 promoter in tumors using the 454 Life Sciences FLX sequencer, and 3) the use of sample-specific DNA barcodes with ..
  17. The Familial Colorectal Neoplasia Collaborative Group
    STEPHEN NORMAN THIBODEAU; Fiscal Year: 2011
    ..support 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 ..
  18. 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...
  19. 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 ..
  20. DNA METHYLATION IN ENDOMETRIAL CANCER
    Soma Das; Fiscal Year: 2000
    ..an important role in the pathogenesis of endometrial carcinoma, and propose to study four cancer-related genes, hMLH1, HMSH2, PTEN, and P16 for hypermethylation...
  21. Role of Kruppel-Like Factor 4 in Wnt and Notch Signaling in the Intestinal Tract
    Amr Ghaleb; Fiscal Year: 2010
    ..or germ-line 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...
  22. 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...
  23. KAREN MICHELE BERKOWITZ; Fiscal Year: 2016
    ..Repair of DNA double strand breaks is delayed, and these persist into diplonema. In addition, MLH1 foci (markers of DNA crossovers) are decreased in pachynema, suggesting a defect in crossover formation...
  24. Molecular Genetics of Colorectal Cancer Progression in a Diverse Patient Cohort
    BROOKE E SYLVESTER; Fiscal Year: 2011
    ..b>MLH1, MSH2, MSH6 and PMS2 are proteins expressed by mismatch repair genes that are responsible for repairing nucleotide ..
  25. Neil Hunter; Fiscal Year: 2016
    ..These include mismatch repair factors, Exo1, Mlh1 and Mlh3;XPF-family nuclease, Mus81-Mms4;Slx4, which forms two distinct nuclease complexes;the recently identified ..
  26. The Colon Cancer Family Registry: Hawaii
    Loic Le Marchand; Fiscal Year: 2011
    ..MSI) 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...
  27. Single Molecule Studies of Recombination and Chromosome Pairing in Meiosis
    Richard Fishel; Fiscal Year: 2013
    ..The MutL homologs (MLH) MLH1-MLH3 specifically interact with MSH4-MSH5 and ultimately appear to determine which of the DSB repair events results ..
  28. PAULA ELAINE COHEN; Fiscal Year: 2016
    ..The MutL homologs of the DNA mismatch repair (MMR) family, MLH1 and MLH3, localize along meiotic chromosomes during prophase I in yeast, zebrafish, mouse and human...
  29. The Colon Cancer Family Registry: Seattle
    Polly A Newcomb; Fiscal Year: 2011
    ..Characterization 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 ..
  30. 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...
  31. 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 ..
  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. 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...
  34. 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...
  35. Fay Kastrinos; Fiscal Year: 2014
    ..developed for Lynch Syndrome: MMRpredict, MMRpro, and PREMM1,2,6 (prediction of mismatch repair gene mutations in MLH1, MSH2, and MSH6)...
  36. Ajay Goel; Fiscal Year: 2016
    ..Methylation-induced silencing of the MLH1 gene occurs because of a CpG island in its promoter, and accounts for about 12% of CRCs...
  37. IMMUNITY IN TRANSGENIC MICE
    Erik Selsing; Fiscal Year: 2010
    ..Second, the roles of the Mlh1 and Exo1 mismatch repair proteins in switching will be compared to the role of Msh2 to determine whether these ..
  38. PAULA ELAINE COHEN; Fiscal Year: 2015
    ..The class I pathway is regulated by the meiotic components of the DNA Mismatch repair (MMR) family (MSH4-MSH5 and MLH1-MLH3 heterodimers), while the class II pathway is regulated by MUS81-EME1...
  39. Non-nucleoside inhibitors of DNA methyl transferase I
    Nigel D Priestley; Fiscal Year: 2013
    ..In this application we seek to demonstrate that we can develop potent and selective inhibitors of Dnmt-1. We further seek to demonstrate that our inhibitors cause reactivation of a model epigenetically silenced gene, human MLH1.
  40. Prognostic Molecular Markers of Colorectal Cancer
    Upender Manne; Fiscal Year: 2009
    ..In addition, the tissue array sections will be evaluated for the expression of hMLH1 and hMSH2 to determine DNA mismatch repair deficient tumors...
  41. 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...
  42. 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...
  43. 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...
  44. 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 ..
  45. 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-..
  46. Junjie Chen; Fiscal Year: 2016
    ..In addition, we demonstrated that Chfr deficiency greatly promoted tumorigenesis in MLH1-deficient mice, suggesting that chromosomal instability caused by Chfr deficiency may synergize with microsatellite ..
  47. 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...
  48. 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) ..
  49. Steven M Lipkin; Fiscal Year: 2014
    ..Briefly, mammalian MLH/PMS proteins heterodimerize to form three distinct complexes, MLH1/PMS1, MLH1/PMS2 and MLH1/MLH3. These complexes interact with MSH2/MSH6 and MSH2/MSH6 heterodimers...
  50. 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...
  51. EDRN: Clinical Epidemiology & Validation Centers
    Henry T Lynch; Fiscal Year: 2010
    ..a study of the frequency of CDKN2A, MGMT, HLTF, APC, HIC1, p14 ARF, MINT31, MINT2, TIMP3, THBS1, and MLH1 methylation in Lynch syndrome colon adenomas and early colorectal cancers, and of the value of methylation assays ..
  52. 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 ..
  53. Mismatch Repair and Associated Genes in Suppression of GI Adenomas and Carcinomas
    Steven Lipkin; Fiscal Year: 2009
    ..Briefly, mammalian MLH/PMS proteins heterodimerize to form three distinct complexes, MLH1/PMS1, MLH1/PMS2 and MLH1/MLH3, that interact with MSH proteins...
  54. Anasheh Halabi; Fiscal Year: 2014
    ..Aim 2: we will use the same methods to establish the contribution of the MutL complex proteins (MutL Homologue 1 (MLH1) and MLH3) to the rate of repeat expansion...
  55. 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...
  56. DNA Mismatch Repair Deficiency and Leukemia Relapse
    Liya Gu; Fiscal Year: 2010
    ..patients will be analyzed for genetic alterations and epigenetic modifications in key MMR genes such as hMSH2 and hMLH1 using combination technologies of PCR-based single strand conformation polymorphism, DNA sequencing, and ..
  57. Calcium, Vitamin D, and Markers of Adenomatous Polyps
    Roberd Bostick; Fiscal Year: 2006
    ..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-term ..
  58. MED1 MUTATIONS IN COLORECTAL CANCER
    Alfonso Bellacosa; Fiscal Year: 2002
    ..In a yeast two-hybrid screening with the mismatch repair protein MLH1 as "bait", we cloned MED1, a novel human DNA repair gene...
  59. 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...
  60. 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...
  61. 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...
  62. Transcriptional Regulation in hMLH1-Silenced Colon Cells
    W Sedwick; Fiscal Year: 2007
    ..Detailed microarray analyses in our laboratory of a human colon tumor cell line in which the mismatch repair gene, hMLH1 is aberrantly silenced for expression have defined a set of genes on chromosome 3 that are co-induced for ..