Genomes and Genes
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
Publications304 found, 100 shown here
- Evidence for heritable predisposition to epigenetic silencing of MLH1Huiping Chen
Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
Int J Cancer 120:1684-8. 2007Epigenetic silencing of MLH1 is the most common cause of defective DNA mismatch repair in endometrial and colorectal cancers...
- Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristicsSven 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...
- Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genesV Pensotti
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milano, Italy
Genes Chromosomes Cancer 19:135-42. 1997Fourteen 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 ..
- Polymorphisms in hMLH1 and risk of early-onset lung cancer in a southeast Chinese populationYu 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...
- Racial differences in MLH1 and MSH2 mutation: an analysis of yellow race and white race based on the InSiGHT databaseWenqian 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. 2010MLH1 and MSH2 mutations underlie 90% of hereditary nonpolyposis colorectal cancer (HNPCC) mutations...
- Functional effects of the MLH1-93G>A polymorphism on MLH1/EPM2AIP1 promoter activitySheron 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 ..
- The association between MLH1 -93 G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysisXin 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...
- MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studiesJia Li Xu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Asian Pac J Cancer Prev 13:901-7. 2012Cumulative 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...
- Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variantsConstanze 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...
- Mutually exclusive promoter hypermethylation patterns of hMLH1 and O6-methylguanine DNA methyltransferase in colorectal cancerEdward 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)...
- Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screeningJenny N Poynter
Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033 9176, USA
Cancer Epidemiol Biomarkers Prev 17:3208-15. 2008Microsatellite 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...
- Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancerC E Bronner
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201 3098
Nature 368:258-61. 1994..DNA mismatch repair gene homologue hMSH2, on chromosome 2p is involved in hereditary non-polyposis colon cancer (HNPCC). On the basis of linkage data, a second HNPCC locus was assigned to chromosome 3p21-23 (ref. 3)...
- MLH1 -93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancerStavroula 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...
- Multiplex SNaPshot genotyping for detecting loss of heterozygosity in the mismatch-repair genes MLH1 and MSH2 in microsatellite-unstable tumorsMaria Bujalkova
Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Bratislava, Slovakia
Clin Chem 54:1844-54. 2008In 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 ..
- Mutation of a mutL homolog in hereditary colon cancerN Papadopoulos
Johns Hopkins Oncology Center, Baltimore, MD 21231
Science 263:1625-9. 1994Some cases of hereditary nonpolyposis colorectal cancer (HNPCC) are due to alterations in a mutS-related mismatch repair gene...
- -93G-->A polymorphism of hMLH1 and risk of primary lung cancerSun 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...
- 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...
- Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome populationMef 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...
- CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutationsY 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 ..
- Use of SSCP analysis to identify germline mutations in HNPCC families fulfilling the Amsterdam criteriaN E Beck
Cancer Genetics and Immunology Laboratory, John Radeliffe Hospital, Headington, Oxford, Oxfordshire, UK
Hum Genet 99:219-24. 1997..Defects in two of the known mismatch repair genes (namely hMSH2 and hMLH1) account for over 90% of mutations found in HNPCC families...
- Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genesM Wehner
Institute of Human Genetics, University of Bonn, Germany
Hum Mutat 10:241-4. 1997
- Characterization of mutator pathway in younger-age-onset colorectal adenocarcinomasSeon 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..e. hMSH2 and hMLH1 in HNPCC, as well as from epigenetic inactivation of hMLH1 in sporadic colorectal tumors...
- Clinicopathological and molecular genetic analysis of HNPCC in ChinaDing Cun Luo
Department of Surgical Oncology, Second People s Hospital of Wenzhou, Wenzhou 325028, Zhejiang Province, China
World J Gastroenterol 11:1673-9. 2005To explore the clinicopathological and molecular genetic features of hereditary nonpolyposis colorectal cancer (HNPCC) in Chinese population.
- Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer familiesXu 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. 2006To 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.
- Two novel germline mutations of MLH1 and investigation of their pathobiology in hereditary non-polyposis colorectal cancer families in ChinaChao 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.
- Estrogen stimulates the expression of mismatch repair gene hMLH1 in colonic epithelial cellsPeng 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...
- Alternative splicing of MLH1 messenger RNA in human normal cellsF Charbonnier
Laboratoire de Genetique Moleculaire, Centre Hospitalo Universitaire de Rouen, France
Cancer Res 55:1839-41. 1995The 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 ..
- Characterization of MLH1 and MSH2 alternative splicing and its relevance to molecular testing of colorectal cancer susceptibilityM Genuardi
Istituto di Genetica Medica, Universita Cattolica del Sacro Cuore, Rome, Italy
Hum Genet 102:15-20. 1998The 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 ..
- Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancerMelissa 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...
- Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patientsHeather 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...
- Promoter hypermethylation is the predominant mechanism in hMLH1 and hMSH2 deregulation and is a poor prognostic factor in nonsmoking lung cancerHan 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...
- Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patientsAndrea 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...
- 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)...
- Founding mutations and Alu-mediated recombination in hereditary colon cancerM Nystrom-Lahti
Department of Medical Genetics, University of Helsinki, Finland
Nat Med 1:1203-6. 1995By 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 ..
- Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16J Wijnen
MGC Department of Human Genetics, Medical Genetics Center, Sylvius Laboratory, Leiden University, The Netherlands
Am J Hum Genet 58:300-7. 1996Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant cancer susceptibility condition. Inherited mutations in at least four DNA mismatch repair genes, hMSH2, hMLH1, hPMS1, and hPMS2, are known to cause HNPCC...
- Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesisC 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...
- The interaction of the human MutL homologues in hereditary nonpolyposis colon cancerS 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. 1999Germline mutations in two human mismatch repair (MMR) genes, hMSH2 and hMLH1, appear to account for approximately 70% of the common cancer susceptibility syndrome hereditary nonpolyposis colorectal cancer (HNPCC)...
- Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression systemJoerg Trojan
Second Department of Medicine, Johann Wolfgang Goethe University, Frankfurt a M, Germany
Gastroenterology 122:211-9. 2002Germline mutations in the DNA mismatch repair (MMR) genes hMLH1 and hMSH2 are associated with susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC)...
- hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancerBenedito 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. 2002The 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).
- MSI in endometrial carcinoma: absence of MLH1 promoter methylation is associated with increased familial risk for cancersAlison 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...
- Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPAC 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...
- BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genesEnric 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...
- Genomic rearrangements in MSH2 and MLH1 are rare mutational events in Spanish patients with hereditary nonpolyposis colorectal cancerSergi 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...
- Analysis of the human MutLalpha.MutSalpha complexGuido 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...
- Common variants in mismatch repair genes and risk of invasive ovarian cancerHonglin 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)...
- Single-nucleotide polymorphisms of mismatch repair genes in healthy Chinese individuals and sporadic colorectal cancer patientsQian 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...
- Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in GermanyC Lamberti
Department of Internal Medicine I, University of Bonn, Bonn, Germany
Digestion 74:58-67. 2006Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC)...
- Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assaysMasanobu 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...
- 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. 2008The 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 ..
- Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancerRebecca 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...
- The interplay between hMLH1 and hMRE11: role in MMR and the effect of hMLH1 mutationsNianxi 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...
- Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutationsE Barrow
Department of General Surgery, Manchester Royal Infirmary, Manchester, UK
Clin Genet 74:233-42. 2008Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition caused by inactivating mutations of DNA mismatch repair (MMR) genes...
- Redundant DNA methylation in colorectal cancers of Lynch-syndrome patientsAster 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...
- Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United StatesFay Kastrinos
Division of Gastroenterology, Brigham and Women s Hospital, Boston, Massachusetts, Boston, MA 02115, USA
Cancer Epidemiol Biomarkers Prev 17:2044-51. 2008Lynch 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 ..
- Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutationsR 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...
- MSH2 and MLH1 mutations in sporadic replication error-positive colorectal carcinoma as assessed by two-dimensional DNA electrophoresisY 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...
- Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC familiesQ 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...
- Enhanced detection of deleterious and other germline mutations of hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindredsS Nomura
Division of Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan
Biochem Biophys Res Commun 271:120-9. 2000..describe a novel and efficient approach for screening mutations of two major HNPCC susceptibility genes, hMSH2 and hMLH1. The system consists of RNA extraction from whole blood treated with the translation inhibitor, followed by long ..
- MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer familiesH F Vasen
Netherlands Foundation for the Detection of Hereditary Tumors, Leiden University Medical Centre
J Clin Oncol 19:4074-80. 2001Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers...
- 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 geneKi Hyuk Shin
Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110 744, Korea
Cancer Res 62:38-42. 2002The human DNA mismatch repair genes hMSH2 and hMLH1 are responsible for the development of hereditary nonpolyposis colorectal cancer (HNPCC)...
- Contribution of human mlh1 and pms2 ATPase activities to DNA mismatch repairGuy Tomer
Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97201, USA
J Biol Chem 277:21801-9. 2002MutLalpha, 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...
- Different molecular mechanisms underlie genomic deletions in the MLH1 GeneAlessandra Viel
Divisione di Oncologia Sperimentale 1, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
Hum Mutat 20:368-74. 2002In 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...
- Hereditary nonpolyposis colorectal cancer: frequent occurrence of large genomic deletions in MSH2 and MLH1 genesYaping Wang
Institute of Human Genetics, University Clinics Bonn, Germany
Int J Cancer 103:636-41. 2003Hereditary nonpolyposis colorectal cancer (HNPCC) is often caused by a deficiency in DNA mismatch repair...
- N-terminus of hMLH1 confers interaction of hMutLalpha and hMutLbeta with hMutSalphaGuido 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...
- Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysisMaran 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....
- Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNAFinn 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...
- Genetic detection of Chinese hereditary nonpolyposis colorectal cancerLong Cui
Department of Colorectal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
World J Gastroenterol 10:209-13. 2004To 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.
- BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testingE 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. 2004According 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 ..
- Ten novel MSH2 and MLH1 germline mutations in families with HNPCCStefan Kruger
Department of Surgical Research, Universitatsklinikum Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
Hum Mutat 24:351-2. 2004Hereditary 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...
- Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasmsJinru 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...
- Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancerGraham 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...
- Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancerElisabeth Mangold
Institute of Human Genetics, University Hospital Bonn, Germany
Int J Cancer 116:692-702. 2005Mutations in DNA MMR genes, mainly MSH2 and MLH1, account for the majority of HNPCC, an autosomal dominant predisposition to colorectal cancer and other malignancies...
- Characterization of hMLH1 and hMSH2 gene dosage alterations in Lynch syndrome patientsLinnea 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...
- Assessment of MLH1 promoter methylation in relation to gene expression requires specific analysisE 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...
- Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: implications for genetic testingJanos Papp
Department Molecular Genetics, National Institute of Oncology, Rath Gy u 7 9, H 1122 Budapest, Hungary
World J Gastroenterol 13:2727-32. 2007To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families.
- Further evidence for heritability of an epimutation in one of 12 cases with MLH1 promoter methylation in blood cells clinically displaying HNPCCMonika 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)...
- Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factorsP 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...
- MLH1 -93G>A promoter polymorphism and risk of mismatch repair deficient colorectal cancerJames M Allan
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom
Int J Cancer 123:2456-9. 2008Rare 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...
- PMS2 involvement in patients suspected of Lynch syndromeRenée C Niessen
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Genes Chromosomes Cancer 48:322-9. 2009It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families...
- MGMT and MLH1 promoter methylation versus APC, KRAS and BRAF gene mutations in colorectal cancer: indications for distinct pathways and sequence of eventsS de Vogel
Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
Ann Oncol 20:1216-22. 2009..in colorectal cancer (CRC), we investigated whether O6-methylguanine DNA methyltransferase (MGMT) and Human Mut-L Homologue 1 (MLH1) promoter hypermethylation are associated with APC, KRAS and BRAF mutations among 734 CRC patients.
- Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndromeRenée C Niessen
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Genes Chromosomes Cancer 48:737-44. 2009It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters...
- The MLH1 -93 promoter variant influences gene expressionManxue Mei
Department of Feed Science, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnical University, Wuhan, Hubei, China
Cancer Epidemiol 34:93-5. 2010The -93 SNP of MLH1 gene is associated with MLH1 gene methylation in endometrial and colorectal cancers...
- Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancerMiralem Mrkonjic
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
PLoS ONE 5:e13314. 2010We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734) and microsatellite unstable (MSI-H) colorectal cancers (CRCs) in two samples...
- A novel exonic rearrangement affecting MLH1 and the contiguous LRRFIP2 is a founder mutation in Portuguese Lynch syndrome familiesManuela Pinheiro
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal
Genet Med 13:895-902. 2011..Although Lynch syndrome is characterized by marked genetic heterogeneity, some specific mutations are observed at high frequency in well-defined populations or ethnic groups due to founder effects...
- Mismatch repair proteins hMLH1 and hMSH2 are differently expressed in the three main subtypes of sporadic renal cell carcinomaChristine Stoehr
Institute of Pathology, University of Erlangen, Erlangen, Germany
Pathobiology 79:162-8. 2012We studied the role of minor mismatch repair proteins (MMR) human MutL homologue 1 (hMLH1) and human MutS homologue 2 (hMSH2) in the main subtypes of renal cell carcinoma (RCC).
- Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosisInga Hinrichsen
Medizinische Klinik 1, Biomedical Research Laboratory, Johann Wolfgang Goethe Universitat, Frankfurt, Germany
Clin Cancer Res 19:2432-41. 2013Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance...
- The molecular basis of Turcot's syndromeS R Hamilton
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205 2196
N Engl J Med 332:839-47. 1995..Turcot's syndrome is characterized clinically by the concurrence of a primary brain tumor and multiple colorectal adenomas. We attempted to define the syndrome at the molecular level...
- The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repairG Langland
Department of Molecular Genetics, Biochemistry, and Microbiology and the Howard Hughes Medical Institute, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
J Biol Chem 276:30031-5. 2001..The C terminus of BLM interacts directly with MLH1 in the yeast-two hybrid assay; far Western analysis and co-immunoprecipitations confirmed the interaction...
- Mutations within the hMLH1 and hPMS2 subunits of the human MutLalpha mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutSalphaMarkus Raschle
Institute of Medical Radiobiology, August Forel Strasse 7, Zurich 8008, Switzerland
J Biol Chem 277:21810-20. 2002..hMutLalpha is a heterodimer of the human MutL homologues hMLH1 and hPMS2, and we decided to exploit its asymmetry to study this function...
- Human mismatch-repair protein MutL homologue 1 (MLH1) interacts with Escherichia coli MutL and MutS in vivo and in vitro: a simple genetic system to assay MLH1 functionBarbara Quaresima
Dipartimento di Medicina Sperimentale e Clinica G Salvatore, Università degli Studi di Catanzaro Magna Graecia, Via Tommaso Campanella 115, 88100 Catanzaro, Italy
Biochem J 371:183-9. 2003..system has been developed to test the effect of over-expression of wild-type or mutated human MutL homologue 1 (hMLH1) proteins on methyl-directed mismatch repair (MMR) in Escherichia coli...
- A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutationsEmiko Kondo
Department of Molecular Pathology, Tohoku University School of Medicine, Miyagi 980 8575, Japan
Cancer Res 63:3302-8. 2003Germ-line mutations in the hMLH1 gene are the most frequent cause of hereditary nonpolyposis colorectal cancer and are characterized by missense mutations at high frequency...
- Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer familiesYoung Kyoung Shin
Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, 110 744, Korea
Hum Mutat 24:351. 2004Hereditary 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...
- Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domainAaron R Ellison
BitTech, Inc, Westlake Village, CA 91361, USA
Nucleic Acids Res 32:5321-38. 2004..repair (MMR) genes MSH2 and MLH1 are responsible for the majority of hereditary non-polyposis colorectal cancer (HNPCC), an autosomal-dominant early-onset cancer syndrome...
- Characterization of the nuclear import of human MutLalphaA Brieger
Medizinische Klinik I, Klinikum der Johann Wolfgang Goethe Universitat, Frankfurt a M, Germany
Mol Carcinog 43:51-8. 2005..b>hMLH1 contains two clusters of positively charged amino acids, which are candidate NLS sequences (aa 469-472 and 496-499)..
- Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast AsiaS C Lee
Department of Haematology Oncology, National University Hospital, Singapore
Clin Genet 68:137-45. 2005..Hereditary non-polyposis colorectal cancer (HNPCC), predominantly due to germline MLH1/MSH2 mutations, is the commonest form of hereditary colorectal cancer (CRC), ..
- Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative StudyJae 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. 2006The 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).
- MSH6 germline mutations in early-onset colorectal cancer patients without family history of the diseaseC Pinto
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal
Br J Cancer 95:752-6. 2006Germline MLH1 and MSH2 mutations are scarce in young colorectal cancer patients with negative family history of the disease...
- Endometrial cancer risk is associated with variants of the mismatch repair genes MLH1 and MSH2Mario E Beiner
Centre for Research in Women s Health, 790 Bay Street, Toronto, Ontario, Canada
Cancer Epidemiol Biomarkers Prev 15:1636-40. 2006..Three single-nucleotide polymorphisms were selected in the MLH1 and MSH2 mismatch repair genes. All the various 672 women with endometrial cancer and 880 controls were genotyped...
- Mismatch repair gene mutations in Chinese HNPCC patientsJ 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...
- MLH1 promoter germline-methylation in selected probands of Chinese hereditary non-polyposis colorectal cancer familiesHeng Hua Zhou
Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China
World J Gastroenterol 14:7329-34. 2008To detect the MLH1 gene promoter germline-methylation in probands of Chinese hereditary nonpolyposis colorectal cancer (HNPCC), and to evaluate the role of methylation in MLH1 gene promoter and molecular genetics in screening for HNPCC.
- Promoter hypermethylation of mismatch repair genes, hMLH1 and hMSH2 in oral squamous cell carcinomaR Czerninski
Department of Oral Medicine, Hebrew University Hadassah School of Dental Medicine, Jerusalem, Israel
Oral Dis 15:206-13. 2009..We therefore wanted to test whether hypermethylation of MMR genes (hMLH1, hMSH2) could contribute to oral carcinogenesis by correlating the information to patient clinical data.
- INHIBITION OF SPONTANEOUS MUTATION IN MISMATCH MUTATORSCatherine 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 ..
- 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...
- NEW HUMAN DNA REPAIR ENDONUCLEASEAlfonso Bellacosa; Fiscal Year: 2002..By employing the yeast interaction trap with hMLH1 as bait , MED1 (mismatch repair endonuclease1), a novel human gene encoding a protein with homology to bacterial ..
- 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 ..
- 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...
- MOLECULAR GENETIC ALTERATIONS OF ENDOMETRIAL CARCINOMALORA ELLENSON; Fiscal Year: 1999..HNPCC has recently been found to be caused by mutations in DNA mismatch repair genes, hMSH2 or hMLH1, resulting in a molecular phenotype characterized by instability of microsatellite sequences...
- 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 ..
- ERIC E ALANI; Fiscal Year: 2016..significant increases (~1000X) in mutation rate and have been implicated in hereditary forms of colon cancer (HNPCC)...
- Mechanistic studies of DNA repair and damage responseDorothy 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-..
- Mismatch Repair Functions Affected During TumorigenesisChristopher 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...
- 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...
- 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...
- 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)...
- Genetics/microsatellite instability in tumor suppressorsHanlee 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 ..
- Screening Pretest for HNPCCJeremy 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...
- METHYLMAP: A TECHNOLOGY TO ANALYZE PROMOTER METHYLATION IN MICRODISSECTED CELLSRobi 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 ..
- The Familial Colorectal Neoplasia Collaborative GroupSTEPHEN 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 ..
- INHERITED MSH6 MUTATIONS IN DIVERSE COLORECTAL CANCERSSapna 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...
- The Microsatellite Instability PhenotypeMICHAEL SICILIANO; Fiscal Year: 2007DESCRIPTION (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 ..
- DNA METHYLATION IN ENDOMETRIAL CANCERSoma 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...
- Role of Kruppel-Like Factor 4 in Wnt and Notch Signaling in the Intestinal TractAmr 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...
- Escherichia coli and Colorectal CarcinogenesisMichael S Donnenberg; Fiscal Year: 2010..coli (AEEC) strains specifically down-regulate expression of mismatch repair (MMR) proteins MLH1 and MSH2...
- 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...
- Molecular Genetics of Colorectal Cancer Progression in a Diverse Patient CohortBROOKE E SYLVESTER; Fiscal Year: 2011..b>MLH1, MSH2, MSH6 and PMS2 are proteins expressed by mismatch repair genes that are responsible for repairing nucleotide ..
- 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 ..
- The Colon Cancer Family Registry: HawaiiLoic 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...
- Single Molecule Studies of Recombination and Chromosome Pairing in MeiosisRichard 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 ..
- 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...
- The Colon Cancer Family Registry: SeattlePolly 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 ..
- 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...
- 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 ..
- The Colon Cancer Family Registry: USC ConsortiumROBERT 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...
- Identifying Conserved Genetic Networks for Eukaryotic MMR GenesWinfried 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...
- 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...
- 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)...
- IMMUNITY IN TRANSGENIC MICEErik 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 ..
- 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...
- 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...
- Non-nucleoside inhibitors of DNA methyl transferase INigel 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.
- Prognostic Molecular Markers of Colorectal CancerUpender 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...
- 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...
- Annual Uterine Cancer Biology SymposiumKAREN 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...
- MULTIPLE RISKS, DECISIONS & BEHAVIORS IN THE GENOMIC ERAKaren 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...
- Genetic Testing and Cancer Screening in Hereditary Cancer SyndromesElena 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 ..
- KATRINA A GODDARD; Fiscal Year: 2015DESCRIPTION (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-..
- 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 ..
- 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...
- Molecular Characterization of Sporadic Colorectal Cancer in the Young from IndiaJonathan 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) ..
- 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...
- MOUSE MODELS FOR HUMAN CANCERRaju 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...
- EDRN: Clinical Epidemiology & Validation CentersHenry 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 ..
- Incorporating genomics into routine clinical care for Veterans with colon cancerSara 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 ..
- Mismatch Repair and Associated Genes in Suppression of GI Adenomas and CarcinomasSteven 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...
- 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...
- Mechanism of PCNA-dependent 5'->3' Mismatch ExcisionGuo 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...
- DNA Mismatch Repair Deficiency and Leukemia RelapseLiya 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 ..
- Calcium, Vitamin D, and Markers of Adenomatous PolypsRoberd 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 ..
- MED1 MUTATIONS IN COLORECTAL CANCERAlfonso 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...
- Prophylactic colectomy intentions in HNPCC patientsKaren Hurley; Fiscal Year: 2005Hereditary 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...
- DNA MISMATCH REPAIR IN EUKARYOTESSatya 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...
- RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCERWalter 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...
- Transcriptional Regulation in hMLH1-Silenced Colon CellsW 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 ..