PMS2

Summary

Gene Symbol: PMS2
Description: PMS1 homolog 2, mismatch repair system component
Alias: HNPCC4, MLH4, PMS2CL, PMSL2, mismatch repair endonuclease PMS2, DNA mismatch repair protein PMS2, PMS1 homolog 2, mismatch repair protein, PMS1 protein homolog 2, PMS2 postmeiotic segregation increased 2, postmeiotic segregation increased 2 nirs variant 6
Species: human

Top Publications

  1. pmc Human postmeiotic segregation 2 exhibits biased repair at tetranucleotide microsatellite sequences
    Sandeep N Shah
    Department of Pathology, Gittlen Cancer Research Foundation and Intercollege Graduate Degree Program in Genetics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Cancer Res 69:1143-9. 2009
  2. ncbi Homozygous PMS2 germline mutations in two families with early-onset haematological malignancy, brain tumours, HNPCC-associated tumours, and signs of neurofibromatosis type 1
    Stefan Kruger
    Department of Surgical Research, Dresden University of Technology, Dresden, Germany
    Eur J Hum Genet 16:62-72. 2008
  3. ncbi Mutations of two PMS homologues in hereditary nonpolyposis colon cancer
    N C Nicolaides
    Johns Hopkins Oncology Center, Baltimore, Maryland 21231
    Nature 371:75-80. 1994
  4. ncbi Genomic organization of the human PMS2 gene family
    N C Nicolaides
    Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA
    Genomics 30:195-206. 1995
  5. ncbi Analysis of the 5' region of PMS2 reveals heterogeneous transcripts and a novel overlapping gene
    N C Nicolaides
    Howard Hughes Medical Institute, Baltimore, Maryland 21231, USA
    Genomics 29:329-34. 1995
  6. 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
  7. pmc BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures
    Y Wang
    Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:927-39. 2000
  8. pmc Interaction of mismatch repair protein PMS2 and the p53-related transcription factor p73 in apoptosis response to cisplatin
    Hideki Shimodaira
    Ludwig Institute for Cancer Research, University of California at San Diego, Bonner Hall 3326, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 100:2420-5. 2003
  9. ncbi A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutations
    Emiko Kondo
    Department of Molecular Pathology, Tohoku University School of Medicine, Miyagi 980 8575, Japan
    Cancer Res 63:3302-8. 2003
  10. 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

Research Grants

  1. Mechanistic studies of DNA repair and damage response
    Dorothy A Erie; Fiscal Year: 2010
  2. PCNA clamp mechanisms in DNA replication and repair
    Manju M Hingorani; Fiscal Year: 2010
  3. Sapna Syngal; Fiscal Year: 2016
  4. Polly A Newcomb; Fiscal Year: 2014
  5. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2016
  6. Molecular Genetics of Colorectal Cancer Progression in a Diverse Patient Cohort
    BROOKE E SYLVESTER; Fiscal Year: 2011
  7. The Familial Colorectal Neoplasia Collaborative Group
    STEPHEN NORMAN THIBODEAU; Fiscal Year: 2011
  8. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2016
  9. IMMUNITY IN TRANSGENIC MICE
    Erik Selsing; Fiscal Year: 2010
  10. INHERITED MSH6 MUTATIONS IN DIVERSE COLORECTAL CANCERS
    Sapna Syngal; Fiscal Year: 2004

Detail Information

Publications220 found, 100 shown here

  1. pmc Human postmeiotic segregation 2 exhibits biased repair at tetranucleotide microsatellite sequences
    Sandeep N Shah
    Department of Pathology, Gittlen Cancer Research Foundation and Intercollege Graduate Degree Program in Genetics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Cancer Res 69:1143-9. 2009
    ..This study also provides clues to possible mechanisms of repair by hPMS2 in the context of the MMR system...
  2. ncbi Homozygous PMS2 germline mutations in two families with early-onset haematological malignancy, brain tumours, HNPCC-associated tumours, and signs of neurofibromatosis type 1
    Stefan Kruger
    Department of Surgical Research, Dresden University of Technology, Dresden, Germany
    Eur J Hum Genet 16:62-72. 2008
    Heterozygous germline mutations in mismatch repair (MMR) genes MLH1, PMS2, MSH2, and MSH6 cause Lynch syndrome...
  3. ncbi Mutations of two PMS homologues in hereditary nonpolyposis colon cancer
    N C Nicolaides
    Johns Hopkins Oncology Center, Baltimore, Maryland 21231
    Nature 371:75-80. 1994
    ..Both hPMS1 and hPMS2 were found to be mutated in the germline of HNPCC patients. This doubles the number of genes implicated in HNPCC and may help explain the relatively high incidence of this disease...
  4. ncbi Genomic organization of the human PMS2 gene family
    N C Nicolaides
    Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA
    Genomics 30:195-206. 1995
    The hPMS2 gene (HGMW-approved symbol PMS2) encodes a mutL homolog that causes hereditary non-polyposis colon cancer (HNPCC) when inherited in mutant form...
  5. ncbi Analysis of the 5' region of PMS2 reveals heterogeneous transcripts and a novel overlapping gene
    N C Nicolaides
    Howard Hughes Medical Institute, Baltimore, Maryland 21231, USA
    Genomics 29:329-34. 1995
    The PMS2 gene encodes a protein that is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC)...
  6. 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
    ....
  7. pmc BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures
    Y Wang
    Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:927-39. 2000
    ..Collectively, these results suggest that BRCA1 may function as a coordinator of multiple activities required for maintenance of genomic integrity during the process of DNA replication and point to a central role for BRCA1 in DNA repair...
  8. pmc Interaction of mismatch repair protein PMS2 and the p53-related transcription factor p73 in apoptosis response to cisplatin
    Hideki Shimodaira
    Ludwig Institute for Cancer Research, University of California at San Diego, Bonner Hall 3326, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 100:2420-5. 2003
    ..Here, we describe an interaction between PMS2, an MMR protein, and p73...
  9. ncbi A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutations
    Emiko Kondo
    Department of Molecular Pathology, Tohoku University School of Medicine, Miyagi 980 8575, Japan
    Cancer Res 63:3302-8. 2003
    ..Thus, this method provides a simple and reliable system for accurate diagnosis of hMLH1 alterations...
  10. 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
    ..Taken together, the results support a model in which hEXO1 plays a role in events at the replication sites as well as a functional role in the MMR and/or recombination processes...
  11. ncbi A defined human system that supports bidirectional mismatch-provoked excision
    Leonid Dzantiev
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 15:31-41. 2004
    ..By contrast, RFC and PCNA have only a limited effect on 5' to 3' excision directed by a 5' strand break...
  12. ncbi Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation
    Hidewaki Nakagawa
    Division of Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, 420 West 12th Avenue, Columbus, OH 43210, USA
    Cancer Res 64:4721-7. 2004
    ..We detected and characterized a new transcript, PMS2CL, showing 98% sequence identity with exons 9 and 11-15 of PMS2 and emanating from a locus close to PMS2 in ..
  13. ncbi Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer
    Kaspar Truninger
    Institute of Molecular Cancer Research, University of Zurich, Switzerland
    Gastroenterology 128:1160-71. 2005
    ..The protein encoded by PMS2 is also essential for MMR; however, alterations in this gene have been documented only in extremely rare cases...
  14. 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...
  15. pmc Human mismatch repair: reconstitution of a nick-directed bidirectional reaction
    Nicoleta Constantin
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:39752-61. 2005
    ..Although this modest inhibition could be because of nonspecific effects, it may indicate limited dependence of bidirectional excision on an aphidicolin-sensitive DNA polymerase...
  16. ncbi Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome)
    Yvonne M C Hendriks
    Center for Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    Gastroenterology 130:312-22. 2006
    The role of the mismatch repair gene PMS2 in hereditary nonpolyposis colorectal carcinoma (HNPCC) is not fully clarified. To date, only 7 different heterozygous truncating PMS2 mutations have been reported in HNPCC-suspected families...
  17. ncbi PMS2 mutations in childhood cancer
    Michel De Vos
    University of Leeds, Yorkshire Regional Genetics Service, United Kingdom
    J Natl Cancer Inst 98:358-61. 2006
    Until recently, the PMS2 DNA mismatch repair gene has only rarely been implicated as a cancer susceptibility locus...
  18. ncbi MutLalpha: at the cutting edge of mismatch repair
    Josef Jiricny
    Institute of Molecular Cancer Research, University of Zurich, CH 8006 Zurich, Switzerland
    Cell 126:239-41. 2006
    ..MutLalpha introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXOI to degrade the strand containing the mismatch...
  19. ncbi Endonucleolytic function of MutLalpha in human mismatch repair
    Farid A Kadyrov
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Cell 126:297-308. 2006
    Half of hereditary nonpolyposis colon cancer kindreds harbor mutations that inactivate MutLalpha (MLH1*PMS2 heterodimer). MutLalpha is required for mismatch repair, but its function in this process is unclear...
  20. 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 (21.7%) were MSI positive (98 of 118 MSI high and 20 of 118 MSI low)...
  21. ncbi RNA-based mutation analysis identifies an unusual MSH6 splicing defect and circumvents PMS2 pseudogene interference
    J Etzler
    Department of Medical Genetics, Medical University Vienna, Vienna, Austria
    Hum Mutat 29:299-305. 2008
    ..detection in the PMS2 gene is severely hampered by the presence of multiple highly similar pseudogenes, including PMS2CL. Using this assay, which is based on direct cDNA sequencing of RT-PCR products, we investigated two families with ..
  22. pmc A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome
    M Clendenning
    Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
    J Med Genet 45:340-5. 2008
    When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (<2% of all identified mutations), yet the immunohistochemical analysis of tumour samples ..
  23. pmc The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations
    Leigha Senter
    Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA
    Gastroenterology 135:419-28. 2008
    ..also known as hereditary nonpolyposis colorectal cancer) has been well described, little is known about disease in PMS2 mutation carriers...
  24. pmc Apoptotic function of human PMS2 compromised by the nonsynonymous single-nucleotide polymorphic variant R20Q
    Ivana Marinovic-Terzic
    Moores Cancer Center, University of California, San Diego, School of Medicine, 3855 Health Sciences Drive, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:13993-8. 2008
    ..It is shown that postmeiotic segregation 2 (PMS2), an MMR protein, is required for cisplatin-induced activation of p73, a member of the p53 family of transcription ..
  25. pmc Functional PMS2 hybrid alleles containing a pseudogene-specific missense variant trace back to a single ancient intrachromosomal recombination event
    Christina Ganster
    Department of Medical Genetics, Medical University Vienna, Austria
    Hum Mutat 31:552-60. 2010
    Sequence exchange between PMS2 and its pseudogene PMS2CL, embedded in an inverted duplication on chromosome 7p22, has been reported to be an ongoing process that leads to functional PMS2 hybrid alleles containing PMS2- and PMS2CL-specific ..
  26. doi Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines
    Johanna C Herkert
    Department of Genetics, University Medical Center Groningen, University of Groningen, P O Box 30 001, 9700 RB Groningen, The Netherlands
    Eur J Cancer 47:965-82. 2011
    Bi-allelic germline mutations of one of the DNA mismatch repair genes, so far predominantly found in PMS2, cause constitutional MMR-deficiency syndrome...
  27. 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
    ..promoter methylation status and the expression of MGMT and the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 in pairs of primary and recurrent glioblastomas of 80 patients, including 64 patients treated with radiotherapy and ..
  28. 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...
  29. pmc Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome
    Michel De Vos
    Molecular Medicine Unit, University of Leeds, Leeds LS9 7TF, United Kingdom
    Am J Hum Genet 74:954-64. 2004
    ..However, autozygosity mapping indicated linkage to a region of 7p22 surrounding the PMS2 mismatch-repair gene. Sequencing of genomic PCR products initially failed to identify a PMS2 mutation...
  30. ncbi Isolated loss of PMS2 expression in colorectal cancers: frequency, patient age, and familial aggregation
    Sharlene Gill
    British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    Clin Cancer Res 11:6466-71. 2005
    ..The genetic deficiency leading to the MSI-H phenotype in such cases is unknown. PMS2 is another member of the DNA mismatch repair complex...
  31. ncbi Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely cause of PMS2 gene inactivation
    Jessie Auclair
    Centre Leon Berard, Unité d Oncologie Moléculaire, Lyon, France
    Hum Mutat 28:1084-90. 2007
    ..carrying compound heterozygous mutations in the MSH6 gene; and the other, compound heterozygous mutations in the PMS2 gene. Interestingly, the inactivation of one PMS2 allele was likely caused by gene conversion...
  32. doi The PMS2 subunit of human MutLalpha contains a metal ion binding domain of the iron-dependent repressor protein family
    Jan Kosinski
    Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, Trojdena 4, 02 109 Warsaw, Poland
    J Mol Biol 382:610-27. 2008
    ..Finally, we demonstrate that the conserved residues of the metal ion binding domain are crucial for MMR activity of MutLalpha in vitro...
  33. ncbi Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX
    Mary Mac Partlin
    Department of Medical Oncology, Glasgow University, UK
    Oncogene 22:819-25. 2003
    ..The effect on HGPRT mutation rate is small (2-3-fold), but is consistent with deregulated c-MYC expression partially inhibiting MMR activity...
  34. ncbi Clinical implications of advances in the molecular genetics of colorectal cancer
    H T Lynch
    Department of Preventive Medicine, Creighton University School of Medicine, Omaha, Nebraska 68179, USA
    Tumori 81:19-29. 1995
    ..PMS1 at chromosome 2p and PMS2 2 at chromosome 7q have also been implicated in HNPCC's etiology...
  35. ncbi Expression of deoxyribonucleic acid repair enzymes during spermatogenesis in mice
    L L Richardson
    Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996 0840, USA
    Biol Reprod 62:789-96. 2000
    ..reverse transcription-polymerase chain reaction approach to identify germ cell transcripts for the MutL homologue, Pms2, and two members of the MutS family, Msh2 and Msh3...
  36. pmc Giant virus with a remarkable complement of genes infects marine zooplankton
    Matthias G Fischer
    Department of Microbiology, University of British Columbia, Vancouver, BC, Canada V6T 1Z4
    Proc Natl Acad Sci U S A 107:19508-13. 2010
    ..CroV is a highly complex marine virus and the only virus studied in genetic detail that infects one of the major groups of predators in the oceans...
  37. doi [How can we diagnose and better understand inflammatory myopathies? The usefulness of auto-antibodies]
    Jean Sibilia
    CHU de Strasbourg, Hopital Hautepierre, Service de Rhumatologie, Laboratoire d Immunologie, 67098 Strasbourg Cedex, France
    Presse Med 39:1010-25. 2010
    ..Other auto-antibodies are directed against nuclear auto-antigens: the anti-Mi-2, anti-PMS (PMS1, PMS2) and related antibodies (MLH1, DNA PKcs…), anti-56 kDa, anti-MJ (NXP-2), anti-SAE and anti-p155/p140 (TIF-1γ)...
  38. ncbi Paternal exposure to cyclophosphamide induces DNA damage and alters the expression of DNA repair genes in the rat preimplantation embryo
    W Harrouk
    Departments of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec, Canada
    Mutat Res 461:229-41. 2000
    ..transcripts for specific members of the nucleotide excision repair family (XPC) and mismatch repair family (MSH2, PMS2) were elevated greatly in control embryos compared to embryos sired by drug-treated males; in contrast, transcripts ..
  39. ncbi A novel trinuclear platinum complex overcomes cisplatin resistance in an osteosarcoma cell system
    P Perego
    Division of Experimental Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
    Mol Pharmacol 55:528-34. 1999
    ..ICL) formation and DNA platination, microsatellite instability, and reduced expression of the DNA mismatch repair protein PMS2. Despite BBR 3464 charge and molecular size, in U2-OS and U2-OS/Pt cells, BBR 3464 accumulation and ..
  40. ncbi Impact of mismatch repair deficiency on genomic stability in the maternal germline and during early embryonic development
    Jon S Larson
    Department of Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267 0524, USA
    Mutat Res 556:45-53. 2004
    The effects of lack of the mismatch repair protein PMS2 on germline and maternal-effect mutations were studied in transgenic mice that allow mutant cells to be visualized in situ...
  41. pmc Patients with an unexplained microsatellite instable tumour have a low risk of familial cancer
    L I H Overbeek
    Department of Human Genetics 849, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
    Br J Cancer 96:1605-12. 2007
    ..for microsatellite instability, MLH1 promoter methylation and/or germline mutations in MLH1, MSH2, MSH6, and PMS2. Characteristics of the 76 families with a germline mutation (24 MLH1, 2 PMS2, 32 MSH2, and 18 MSH6) were compared ..
  42. ncbi Mice defective in the DNA mismatch gene PMS2 are hypersensitive to MNU induced thymic lymphoma and are partially protected by transgenic expression of human MGMT
    X Qin
    Division of Hematology Oncology, Case Western Reserve University, Cleveland, Ohio, OH 44106 4937, USA
    Oncogene 18:4394-400. 1999
    DNA mismatch repair (MMR) stabilizes the cellular genome. Mice defective in the MMR gene PMS2 are susceptible to spontaneous thymic lymphoma and sarcomas...
  43. pmc Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans
    Oliver D K Maddocks
    Division of Pathology, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
    PLoS ONE 4:e5517. 2009
    ..We hypothesised that EPEC infection could influence molecular pathways involved in colorectal tumourigenesis...
  44. pmc Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors
    Nurten Saydam
    Institute of Molecular Cancer Research of the University of Zurich, Switzerland
    Nucleic Acids Res 35:5706-16. 2007
    ..Here we show that WRN physically interacts with the MSH2/MSH6 (MutSalpha), MSH2/MSH3 (MutSbeta) and MLH1/PMS2 (MutLalpha) heterodimers that are involved in the initiation of mismatch repair (MMR) and the rejection of ..
  45. doi Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms
    Laura J Tafe
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Mod Pathol 23:781-9. 2010
    ..expression by immunohistochemistry was evaluated in 17 cases, and 8 (47%) were abnormal (7 with loss of MLH1/PMS2 and 1 with MSH6 loss)...
  46. ncbi Analysis of mismatch repair defects in the familial occurrence of lymphoma and colorectal cancer
    J Teruya-Feldstein
    Department of Pathology, Memorial Sloan Kettering Cancer Center, Memorial Hospital, New York, NY 10021, USA
    Leuk Lymphoma 43:1619-26. 2002
    ..These MMR genes include MLH1, MSH2, MSH3, MSH6, PMS1 and PMS2. We sought to analyze the occurrence of NHL and HD in families with clusters of colorectal cancers (CRC)...
  47. doi Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities
    Karuna Garg
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Am J Surg Pathol 33:925-33. 2009
    ..The rate of IHC abnormality in the younger group was approximately 30% with a nearly equal distribution of MLH1/PMS2 and MSH2/MSH6 abnormalities. In the older age group, TM-MMR triggered IHC analysis in 31 of 34 cases...
  48. doi Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome
    C P Kratz
    Division of Clinical Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University Innsbruck, Schoepfstr 41, 6020 Innsbruck, Austria
    J Med Genet 46:418-20. 2009
    Biallelic germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterised by early-onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1)...
  49. ncbi Homozygous PMS2 deletion causes a severe colorectal cancer and multiple adenoma phenotype without extraintestinal cancer
    Olivia Will
    Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research, London, UK
    Gastroenterology 132:527-30. 2007
    ..He also had dysmorphic features, mental retardation, and café-au-lait spots but no brain tumor. We aimed to establish his molecular diagnosis...
  50. ncbi BRCA1 activates a G2-M cell cycle checkpoint following 6-thioguanine-induced DNA mismatch damage
    Kazuhiko Yamane
    Department of Radiation Oncology, Case Western Reserve University and Case Comprehensive Cancer Center University Hospitals Case Medical Center, Cleveland, Ohio 44106 6068, USA
    Cancer Res 67:6286-92. 2007
    ..The MMR proteins MSH2, MSH6, MLH1, and PMS2 are similarly detected in both cell lines...
  51. doi A homozygote splice site PMS2 mutation as cause of Turcot syndrome gives rise to two different abnormal transcripts
    Wenche Sjursen
    Department of Pathology and Medical Genetics, St Olavs University Hospital, Erling Skjalgssons gt 1, 7006 Trondheim, Norway
    Fam Cancer 8:179-86. 2009
    ..cDNA analysis was carried out for the mismatch repair gene PMS2. The patients genotype was found to be a homozygous splice site mutation in the PMS2 gene, c...
  52. pmc Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers
    Katarina Zavodna
    Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic
    BMC Cancer 9:405. 2009
    ..We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts...
  53. ncbi Modulation of error-prone double-strand break repair in mammalian chromosomes by DNA mismatch repair protein Mlh1
    Laura A Bannister
    Department of Biological Sciences, University of South Carolina, 700 Sumter Street, Columbia, SC 29208, USA
    DNA Repair (Amst) 3:465-74. 2004
    ..Collectively, our results suggest that Mlh1 modulates error-prone NHEJ by inhibiting the annealing of DNA ends containing noncomplementary base pairs or by promoting the annealing of microhomologies...
  54. pmc TGF-beta signaling alterations and susceptibility to colorectal cancer
    Yanfei Xu
    Cancer Genetics Program, Division of Hematology Oncology, Department o Medicine, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Hum Mol Genet 16:R14-20. 2007
    ..all colorectal cancer cases, a fraction higher than that attributable to mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Furthermore, TGFBR1*6A is emerging as a potent modifier of colorectal cancer risk among individuals with a strong ..
  55. doi Microsatellite instability and mismatch repair protein defects in ovarian epithelial neoplasms in patients 50 years of age and younger
    Kristin C Jensen
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Am J Surg Pathol 32:1029-37. 2008
    ..D5S346, and D17S250) and deficiency of MMR protein expression by immunohistochemistry (MLH1, MSH2, MSH6, and PMS2)...
  56. doi Baseline expression profile of meiotic-specific genes in healthy fertile males
    Carme Nogues
    Departament Biologia Cel lular, Fisiologia i Immunologia, Universitat Autonoma Barcelona, Bellaterra, Spain
    Fertil Steril 92:578-82. 2009
    To establish the quantitative gene-expression profile of nine meiotic genes involved in synapsis and chromosome cohesion (SYCP1, SPO11, MSH4, MSH5, MLH1, MLH3, PMS2, STAG3, and REC8) in healthy fertile males.
  57. doi Compromised repair of clustered DNA damage in the human acute lymphoblastic leukemia MSH2-deficient NALM-6 cells
    Stewart M Holt
    Department of Biology, Thomas Harriot College of Arts and Sciences, East Carolina University, Greenville, NC 27858, USA
    Mutat Res 674:123-30. 2009
    ..Our studies suggest that MSH2 is probably involved in the processing of the biologically significant clustered DNA damages as well as the execution of apoptosis induced by ionizing radiation...
  58. pmc Genome-scale identification method applied to find cryptic aminoglycoside resistance genes in Pseudomonas aeruginosa
    Julie M Struble
    Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA
    PLoS ONE 4:e6576. 2009
    ..Improving understanding of the evolution and genetic basis of resistance is a fundamental goal in the field of microbiology...
  59. pmc Hijacked DNA repair proteins and unchained DNA polymerases
    Huseyin Saribasak
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Philos Trans R Soc Lond B Biol Sci 364:605-11. 2009
    ..In the mutagenic pathway, we first studied the role of mismatch repair proteins, MSH2, MSH3, MSH6, PMS2 and MLH1, since they would recognize mismatches...
  60. ncbi Heterozygous DNA mismatch repair gene PMS2-knockout mice are susceptible to intestinal tumor induction with N-methyl-N-nitrosourea
    X Qin
    Division of Hematology Oncology and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106 4937, USA
    Carcinogenesis 21:833-8. 2000
    b>PMS2-deficient (PMS2(-/-)) mice are hypersensitive to N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas based on the failure to initiate mismatch repair (MMR) at O(6)-methylguanine:T mismatches formed after MNU exposure...
  61. ncbi Transgenic expression of human MGMT blocks the hypersensitivity of PMS2-deficient mice to low dose MNU thymic lymphomagenesis
    X Qin
    Division of Hematology Oncology and the Ireland Cancer Center, Case Western Reserve University, Cleveland, OH 44106 4937, USA
    Carcinogenesis 20:1667-73. 1999
    Mice deficient in the DNA mismatch repair (MMR) gene, PMS2, develop spontaneous thymic lymphomas and sarcomas. We have previously shown that PMS2(-/-) mice were hypersensitive to a single i.p...
  62. ncbi Hypermutability to ionizing radiation in mismatch repair-deficient, Pms2 knockout mice
    X S Xu
    Departments of Therapeutic Radiology and Genetics, Yale University School of Medicine, New Haven, Connecticut 06520 8040, USA
    Cancer Res 61:3775-80. 2001
    ..this tolerance phenotype would render MMR-deficient animals hypermutable to IR, we compared IR mutagenesis of Pms2-deficient versus wild-type transgenic mice carrying a lambda shuttle vector for mutation detection...
  63. ncbi Ntg2p, a Saccharomyces cerevisiae DNA N-glycosylase/apurinic or apyrimidinic lyase involved in base excision repair of oxidative DNA damage, interacts with the DNA mismatch repair protein Mlh1p. Identification of a Mlh1p binding motif
    Lionel Gellon
    Commissariat a l Energie Atomique, Departement de Radiobiologie et Radiopathologie, UMR217 CNRS CEA Radiobiologie Moléculaire et Cellulaire, Fontenay aux Roses 92265, France
    J Biol Chem 277:29963-72. 2002
    ..Therefore, we propose that the R/K-S-R/K-Y/F-Y/F sequence could define a Mhl1 binding motif. The results also suggest that base excision repair and MMR can cooperate to prevent deleterious effects of oxidative DNA damage...
  64. ncbi Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours
    Andrew Ruszkiewicz
    Institute of Medical and Veterinary Science, Tissue Pathology, Royal Adelaide Hospital, Adelaide, South Australia
    Pathology 34:541-7. 2002
    The aim of this study was to assess the performance of immunohistochemistry using antibodies for MLH1, MSH2, MSH6 and PMS2 mismatch repair gene proteins against microsatellite instability (MSI) testing.
  65. ncbi Frequency and types of spontaneous Hprt lymphocyte mutations in Pms2-deficient mice
    Joseph G Shaddock
    Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, US FDA, Jefferson, AR 72079, USA
    Mutat Res 595:69-79. 2006
    Deficiencies in DNA mismatch repair (MMR) result in predisposition to neoplasia in both rodents and humans. Pms2 is one of the several proteins involved in the eukaryotic MMR system...
  66. ncbi Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma
    Ippolito Modica
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Am J Surg Pathol 31:744-51. 2007
    ..Overall, IHC with MLH1 and MSH2 antibodies detected 69% of MSI-H tumors with a specificity of 100%. Adding PMS2 and MSH6 to the antibody panel increased the sensitivity to 91% but decreased the specificity to 83%...
  67. pmc Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry
    Jinru Shia
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Mol Diagn 10:293-300. 2008
    ..More recent studies that included postmeiotic segregation increased 2 (PMS2) and MSH6, on the other hand, have demonstrated an IHC predictive value that is virtually equivalent to that of MSI ..
  68. pmc Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair
    Jan Kosinski
    Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, Warsaw, Poland
    Hum Mutat 31:975-82. 2010
    ..are located in the C-terminal domain (CTD) of MLH1, which is responsible for constitutive dimerization with PMS2. We analyzed which alterations may result in pathogenic effects due to interference with dimerization...
  69. pmc Family history and molecular features of children, adolescents, and young adults with colorectal carcinoma
    C Durno
    Division of Gastroenterology and Clinical Nutrition, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, Ontario, Canada M5G 1X8
    Gut 54:1146-50. 2005
    ..Colorectal cancer is extremely rare in childhood. Published case series reporting children and adolescents with colorectal cancer have not focused on the underlying genetic aspects of the tumour or genetic susceptibility of the families...
  70. ncbi Analysis of the quaternary structure of the MutL C-terminal domain
    Jan Kosinski
    Institut für Biochemie FB 08, Justus Liebig Universitat, Giessen D 35392, Germany
    J Mol Biol 351:895-909. 2005
    ....
  71. ncbi Genomic rearrangements in MSH2, MLH1 or MSH6 are rare in HNPCC patients carrying point mutations
    Steffen Pistorius
    Department of Visceral, Thoracic and Vascular Surgery, Technische Universitat Dresden, Fetscherstr 74, 01307 Dresden, Germany
    Cancer Lett 248:89-95. 2007
    ..disease with high penetrance, caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, PMS2 and MLH3...
  72. ncbi Microsatellite instability markers for identifying early-onset colorectal cancers caused by germ-line mutations in DNA mismatch repair genes
    Leeanne J Mead
    Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
    Clin Cancer Res 13:2865-9. 2007
    ..We wanted to examine which microsatellite markers currently used to detect MSI best predict early-onset colorectal cancer caused by germ-line mutations in MMR genes...
  73. ncbi Methylation damage response in hematopoietic progenitor cells
    Ida Casorelli
    Section of Experimental Carcinogenesis, Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Rome, Italy
    DNA Repair (Amst) 6:1170-8. 2007
    ..The overexpressed genes included members of the mismatch repair (MMR) (MSH2, MSH6, MLH1, PMS2), base excision repair (AAG, APEX), DNA damage reversal (O(6)-methylguanine DNA methyltransferase) (MGMT), and DNA ..
  74. ncbi Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting
    Lucia I H Overbeek
    Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
    Am J Surg Pathol 32:1246-51. 2008
    ..from 5 different pathology laboratories evaluated 100 molecularly defined colorectal cancers stained for MLH1, PMS2, MSH2, and MSH6...
  75. doi Towards identification of hereditary DNA mismatch repair deficiency: sebaceous neoplasm warrants routine immunohistochemical screening regardless of patient's age or other clinical characteristics
    Lurmag Orta
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Am J Surg Pathol 33:934-44. 2009
    ..with 1 or more sebaceous neoplasms based on the pattern of immunohistochemical expression of MLH1, MSH2, MSH6, and PMS2, and comparatively analyzed their clinical and pathologic characteristics, including tumor-infiltrating lymphocytes ..
  76. pmc Adenosine triphosphate stimulates Aquifex aeolicus MutL endonuclease activity
    Jerome Mauris
    New England Biolabs, Inc, Ipswich, Massachusetts, USA
    PLoS ONE 4:e7175. 2009
    Human PMS2 (hPMS2) homologues act to nick 5' and 3' to misincorporated nucleotides during mismatch repair in organisms that lack MutH. Mn(++) was previously found to stimulate the endonuclease activity of these homologues...
  77. doi Changes in the expression profile of the meiosis-involved mismatch repair genes in impaired human spermatogenesis
    Ernest Terribas
    Medical and Molecular Genetics Center Fundació IDIBELL, L Hospitalet de Llobregat, Barcelona, Spain
    J Androl 31:346-57. 2010
    ..of MMR genes in impaired human spermatogenesis, we performed transcript levels analysis of MMR genes (MLH1, MLH3, PMS2, MSH4, and MSH5), and other meiosis-involved genes (ATR, HSPA2, and SYCP3) as controls, by real-time reverse ..
  78. doi Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma
    Fei Bao
    Department of Pathology, Columbia University Medical Center, Weill Cornell Medical College, New York, NY, USA
    Am J Surg Pathol 34:1798-804. 2010
    ..instability (MSI), and the combined results of mutL homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), mutS homolog 2 (MSH2), or mutS homolog 6 (MSH6) immunostains may point to the defective MMR protein in tumors ..
  79. ncbi Specificity of mutations in the PMS2-deficient human tumor cell line HEC-1-A
    T Kato
    Radiation Biology Center, Kyoto University, Kyoto 606, Japan
    Mutat Res 422:279-83. 1998
    ....
  80. ncbi The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6
    Graziella Pedrazzi
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstr 190, CH 8057 Zurich, Switzerland
    Biol Chem 384:1155-64. 2003
    ....
  81. pmc Localization of MMR proteins on meiotic chromosomes in mice indicates distinct functions during prophase I
    Nadine K Kolas
    Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    J Cell Biol 171:447-58. 2005
    ..Mutations of three of the four MutL homologues (Mlh1, Mlh3, and Pms2) result in meiotic defects...
  82. pmc Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6
    Denise Campisi Hegan
    Department of Therapeutic Radiology, Yale University School of Medicine, PO Box 208040, New Haven, CT 06520 8040, USA
    Carcinogenesis 27:2402-8. 2006
    ..in MMR-deficient mice using two transgenic reporter genes, supFG1 and cII, in the context of mice deficient for Pms2, Mlh1, Msh2, Msh3 or Msh6 or both Msh2 and Msh3 or both Msh3 and Msh6...
  83. pmc Genetic susceptibility to distinct bladder cancer subphenotypes
    Lin T Guey
    Spanish National Cancer Research Centre, Madrid, Spain
    Eur Urol 57:283-92. 2010
    ..It is conceivable that specific patterns of genetic susceptibility are associated with particular subphenotypes...
  84. doi Clinical and histomolecular endometrial tumor characterization of patients at-risk for Lynch syndrome in South of Brazil
    Silvia Liliana Cossio
    Programa de Pós Graduação em Medicina Ciências Gastroenterológicas, Universidade Federal do Rio Grande do Sul UFRGS, Porto Alegre, RS, Brazil
    Fam Cancer 9:131-9. 2010
    ..syndrome caused by germline mutations in one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. Clinically, Lynch syndrome is characterized by early onset (45 years) of colorectal cancer (CRC), as well as extra-..
  85. ncbi Counterpoint: implementing population genetic screening for Lynch Syndrome among newly diagnosed colorectal cancer patients--will the ends justify the means?
    Michael J Hall
    Medical Oncology and Cancer Prevention and Control, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Natl Compr Canc Netw 8:606-11. 2010
    Inherited mutations in 1 of 4 known mismatch repair genes (MLH1, MSH2, MSH6, PMS2) are associated with various cancer risks collectively referred to as Lynch syndrome...
  86. pmc Mutation screening of MSH2 and MLH1 mRNA in hereditary non-polyposis colon cancer syndrome
    N J Froggatt
    Cambridge University, Department of Pathology, UK
    J Med Genet 33:726-30. 1996
    Germline mutations in four human mismatch repair genes (MSH2, MLH1, PMS1, and PMS2) have been reported to cause hereditary non-polyposis colon cancer syndrome (HNPCC)...
  87. ncbi Cancer genetics in the new era of molecular biology
    H T Lynch
    Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska 68178, USA
    Ann N Y Acad Sci 833:1-28. 1997
    ..At least four mutator genes (MHS2, MLH1, PMS1 and PMS2) appear to account for 70-80% of hereditary nonpolypoid colorectal cancer (HNPCC)...
  88. pmc A Uve1p-mediated mismatch repair pathway in Schizosaccharomyces pombe
    B Kaur
    Department of Biochemistry, Graduate Program in Biochemistry and Cell and Developmental Biology, Emory University, School of Medicine, Atlanta, Georgia 30322, USA
    Mol Cell Biol 19:4703-10. 1999
    ..These results suggest that Uve1p has a surprisingly broad substrate specificity and may function as a general type of DNA repair protein with the capacity to initiate mismatch repair in certain organisms...
  89. 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
    ..the interactions of six MLH1 variants, carrying either missense mutations or in-frame deletions, with normal PMS2 and tested the functionality of these heterodimers of MLH1 and PMS2 (MutL(alpha)) in an in vitro MMR assay...
  90. pmc Maternal effect for DNA mismatch repair in the mouse
    Vanessa E Gurtu
    Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA
    Genetics 160:271-7. 2002
    ..Mice deficient in Pms2, a mammalian homolog of bacterial mutL, develop cancer and display MSI in all tissues examined, including the male ..
  91. ncbi Mismatch repair gene mutations in renal cell carcinoma
    Fredrick S Leach
    Urologic Oncology Branch NCI, National Institutes of Health, 10 Center Drive, Bldg 10 Room 2B47, Bethesda, MD 20892 1501, USA
    Cancer Biol Ther 1:530-6. 2002
    ..Genetic alterations affecting expression were limited to MLH1 since other MMR proteins (MSH2, MSH6 and PMS2) were detectable in our RCC lines...
  92. ncbi Apoptosis and mutation in the murine small intestine: loss of Mlh1- and Pms2-dependent apoptosis leads to increased mutation in vivo
    Owen J Sansom
    School of Biosciences, University of Cardiff, Museum Avenue, P O Box 911, Cardiff, Wales CF10 3US, UK
    DNA Repair (Amst) 2:1029-39. 2003
    ..Here, we extend these studies to the MutL homologues (MLH) Mlh1 and Pms2 by analysing the apoptotic response within the small intestine of gene targeted strains...
  93. ncbi Truncation of the C-terminus of human MLH1 blocks intracellular stabilization of PMS2 and disrupts DNA mismatch repair
    Azizah B Mohd
    Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agricultural and Life Sciences Bldg, Corvallis, OR 97331, USA
    DNA Repair (Amst) 5:347-61. 2006
    ..MLH1 functions as a heterodimer with the PMS2 protein, and steady state levels of PMS2 are very low in MLH1-deficient cells...
  94. ncbi The genetics of HNPCC: application to diagnosis and screening
    Wael M Abdel-Rahman
    Department of Medical Genetics, University of Helsinki, Helsinki, Finland
    Crit Rev Oncol Hematol 58:208-20. 2006
    ..primarily due to heterozygous germline mutations in one of the mismatch repair genes; mainly MLH1, MSH2, MSH6 and PMS2. The resulting mismatch repair deficiency leads to microsatellite instability which is the hallmark of tumors ..
  95. pmc Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation
    Sridharan Gururangan
    The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    Neuro Oncol 10:93-7. 2008
    ..He was found to have a possible germline mutation of the PMS2 gene, as evidenced by absent protein expression in both normal and tumor tissues...
  96. pmc Extensive genomic diversity of closely related Wolbachia strains
    Nadeeza Ishmael
    J Craig Venter Institute, 9708 Medical Center Dr, Rockville, MD 20850, USA
    Microbiology 155:2211-22. 2009
    ..Overall, these insect-associated Wolbachia have highly mosaic genomes, with lateral gene transfer playing an important role in their diversity and evolution...
  97. doi Immunohistochemistry as first-line screening for detecting colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: a 2-antibody panel may be as predictive as a 4-antibody panel
    Jinru Shia
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Am J Surg Pathol 33:1639-45. 2009
    ..clinical settings, a 4-antibody panel that includes the 4 most commonly affected proteins (MLH1, MSH2, MSH6, and PMS2) is being used generally...
  98. pmc PCNA function in the activation and strand direction of MutLα endonuclease in mismatch repair
    Anna Pluciennik
    Department of Biochemistry and Howard Hughes Medical Institute, Box 3711, Duke University Medical Center, Durham, NC 27710
    Proc Natl Acad Sci U S A 107:16066-71. 2010
    MutLα (MLH1-PMS2) is a latent endonuclease that is activated in a mismatch-, MutSα-, proliferating cell nuclear antigen (PCNA)-, replication factor C (RFC)-, and ATP-dependent manner, with nuclease action directed to the heteroduplex ..
  99. doi Expression of mismatch repair gene PMS2 in nasopharyngeal carcinoma and regulation by glycogen synthase kinase-3β in vivo and in vitro
    Jugao Fang
    Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
    Auris Nasus Larynx 39:71-6. 2012
    To evaluate the expression of mismatch repair gene PMS2 in human nasopharyngeal carcinoma (NPC) tissues and evaluate the effect of glycogen synthase kinase (GSK)-3β on PMS2 production in vivo and in vitro.
  100. pmc Microsatellite instability and DNA mismatch repair protein deficiency in Lynch syndrome colorectal polyps
    Matthew B Yurgelun
    Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Cancer Prev Res (Phila) 5:574-82. 2012
    ..PCR for five mononucleotide repeat microsatellite markers, and also for expression of MLH1, MSH2, MSH6, and PMS2 proteins by immunohistochemistry...
  101. pmc Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer
    Karin Kast
    Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany
    BMC Cancer 12:531. 2012
    ..Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare.

Research Grants44

  1. Mechanistic studies of DNA repair and damage response
    Dorothy A Erie; Fiscal Year: 2010
    ..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-cycle ..
  2. PCNA clamp mechanisms in DNA replication and repair
    Manju M Hingorani; Fiscal Year: 2010
    ..Knowledge gained from this study will help elucidate how clamps help regulate the critical processes of DNA replication and DNA mismatch repair. ..
  3. Sapna Syngal; Fiscal Year: 2016
    ..Since the development of the model, two additional genes, PMS2 and EPCAM, have been implicated in the condition...
  4. Polly A Newcomb; Fiscal Year: 2014
    ..Participants have: (i) been tested for mutations in the mismatch repair genes (MLH1, MSH2, MSH6 and PMS2) and MUTYH, and measured for the single nucleotide polymorphisms (SNPs) known to be associated with CRC;(ii) ..
  5. 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...
  6. Molecular Genetics of Colorectal Cancer Progression in a Diverse Patient Cohort
    BROOKE E SYLVESTER; Fiscal Year: 2011
    ..MLH1, MSH2, MSH6 and PMS2 are proteins expressed by mismatch repair genes that are responsible for repairing nucleotide mispairs and small ..
  7. The Familial Colorectal Neoplasia Collaborative Group
    STEPHEN NORMAN THIBODEAU; Fiscal Year: 2011
    ..products to other CFR sites for characterization of somatic MLH1 methylation and BRAF analysis, germline PMS2 and MYH mutations;7) maintain local bioinformatics and data transmissions;8) maintain necessary administrative core ..
  8. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2016
    ..syndrome, is caused by germline mutations in one of four DNA mismatch repair (MMR) genes- MLH1, MSH2, MSH6, and PMS2. About 20-30% of the variants identified in MMR and other cancer susceptibility genes are missense or non-coding ..
  9. IMMUNITY IN TRANSGENIC MICE
    Erik Selsing; Fiscal Year: 2010
    ..If ? transgene translocations also do not involve AID then this would provide a convenient model system for genetic analyses of the sequences and proteins important for the IgH translocation process. ..
  10. INHERITED MSH6 MUTATIONS IN DIVERSE COLORECTAL CANCERS
    Sapna Syngal; Fiscal Year: 2004
    ..Mutations in four mismatch repair genes (MSH2, MLH1, PMS1 and PMS2) have been identified primarily in families with hereditary nonpolyposis colorectal cancer (HNPCC) featuring high ..
  11. FAMILIAL COLORECTAL NEOPLASIA COLLABORATIVE GROUP
    Noralane Lindor; Fiscal Year: 2007
    ..products to other CFR sites for characterization of somatic MLH1 methylation\par and BRAF analysis, germline PMS2 and MYH mutations; 7) maintain local bioinformatics and data\par transmissions; 8) maintain necessary ..
  12. The Colon Cancer Family Registry: Australasia
    John L Hopper; Fiscal Year: 2011
    ..and genetic characterization, and in Phase III will conduct all of the Colon CFR mutation testing for BRAF and PMS2 and perform the IHC work for Seattle and DSC consortium registries...
  13. 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...
  14. 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...
  15. LYMPHOMAGENESIS OF O6-METHYLGUANINE
    Stanton Gerson; Fiscal Year: 2002
    ..In the first Specific Aim, transgenic mice defective in one of two mismatch repair proteins, PMS2 or MSH2 will be treated with MNU and followed for induction of tumors...
  16. DNA replication, DNA repair and microsatellite stability
    Kristin Eckert; Fiscal Year: 2009
    ..The ex vivo shuttle vector system will be used in naturally occurring MLH1, PMS2, NBS1 and hMre11-defective lymphoblastoid cell lines, and in cells with gene expression down-regulated by antisense ..
  17. MISMATCH REPAIR PROTEIN, PMS2, AND GENETIC RECOMBINATION
    SEAN BAKER; Fiscal Year: 2002
    ..adapted from investigator's abstract: Male mice homozygous for a null mutation in the DNA mismatch repair gene, Pms2, are sterile and produce only abnormal spermatozoa...
  18. MISMATCH REPAIR DEFECTS AND HUMAN TUMOR RADIOSENSITIZATI
    Timothy Kinsella; Fiscal Year: 2003
    Mutations or loss of expression of DNA mismatch repair (MMR) genes especially MLH1, MSH2 and PMS2) have been found with an increasing frequency in many types of sporadic human colon cancers, along with the causal relationship previously ..
  19. Links between Mismatch Repair and Replication
    Hernan Flores Rozas; Fiscal Year: 2005
    ..coli MutS protein, MSH2, MSH3 and MSH6. Three yeast homologs of E. coli MutL are required for MMR, MLH1, PMS1 (PMS2 in humans) and MLH3...
  20. DNA MISMATCH REPAIR IN FDURD INDUCED CYTOTOXICITY
    David Boothman; Fiscal Year: 2002
    ..Aim 3: To determine if differences in G2/M arrest after FdUrd exposure between cells expressing or lacking MLH1, PMS2, or MSH2 are associated with MMR-mediated creating of DNA double-strand breaks (DSBs). (Years 2-5)...
  21. INTRACHROMOSOMAL RECOMBINATION IN MAMMALIAN CELLS
    ROBERT LISKAY; Fiscal Year: 2009
    Mutation in any one of five human DNA mismatch repair (MMR )gene homologs, MSH2, MSH6,MLH1, PMS2 and PMS1, contributes to both hereditary and spontaneous cancers...
  22. DNA MISMATCH REPAIR GENES AND TUMORIGENESIS
    Tomas Prolla; Fiscal Year: 2003
    ..We have recently generated and characterized mice deficient for the Mlh1, Pms2 and Pms1 DNA mismatch repair gene...
  23. COPING WITH HEREDITARY NON POLYPOSIS COLON CANCER RISK
    Henry Lynch; Fiscal Year: 1999
    ..studies indicate that most HNPCC is attributable to mutations in the mismatch repair genes hMSH2, hMLH1, PMS1 or PMS2. The availability of genetic testing for HNPCC affords an unprecedented opportunity for high risk family members to ..
  24. PHENOTYPIC AND PSYCHOSOCIAL STUDY OF THE L1307K MUTATION
    Henry Lynch; Fiscal Year: 2004
    ....
  25. PREDISPOSING/MODIFYING GENES IN HEREDITARY COLON CANCER
    Paivi Peltomaki; Fiscal Year: 2001
    ..The aim is to identify genes that might modify the clinical phenotype of HNPCC, taking advantage of association and linkage-based approaches in these genetically homogeneous subsets of HNPCC patients. ..
  26. Plasma Microarray Analysis and Ovarian Cancer Biomarkers
    Johnathan Lancaster; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  27. ALTERNATIVE DNA DAMAGE CHECKPOINT PATHWAYS IN EUKARYOTES
    Sharon Plon; Fiscal Year: 2002
    ..These latter results will demonstrate whether activation of an alternative checkpoint pathway might be used therapeutically for patients with AT or to alter the resistance of tumors to radiation and other DNA-damaging agents. ..
  28. P21 INDUCTION BY BRCA2
    Fergus Couch; Fiscal Year: 2002
    ....
  29. MOLECULAR ANALYSIS OF FANCONI'S ANEMIA C PROTEIN
    Sharon Plon; Fiscal Year: 2003
    ....
  30. MOLECULAR ANALYSES OF MLH3 NULL MICE
    Steven Lipkin; Fiscal Year: 2003
    ..genes associated with microsatellite instability have previously been described: MLH1, MSH2, MSH3, MSH6, PMS1, and PMS2. Each one of these genes is associated with genetic susceptibility to cancer in humans (specifically, Hereditary ..
  31. Molecular Profiling to Predict Response to Chemotherapy
    Johnathan Lancaster; Fiscal Year: 2006
    ..Ultimately, defining the biologic underpinnings of response to therapy will facilitate the development of more active agents that may improve cure rates for ovarian cancer. ..
  32. Characterization of the Chromosome 17q23 Amplicon
    Fergus Couch; Fiscal Year: 2006
    ..Thus, the project may involve a complete transition from benchtop to bedside. Finally, the amplified and overexpressed genes may prove useful as important targets of gene, pharmacological, and immunological therapy in the future. ..
  33. A PROGRAM OF RESEARCH IN POPULATION CYTOGENETICS
    Terry J Hassold; Fiscal Year: 2010
    ....
  34. Germline epimutation of hMLH1 as a factor in HNPCC
    David Martin; Fiscal Year: 2006
    ..They may also produce the first clear evidence that epigenetic silencing can be inherited to produce a familial disorder such as HNPCC. [unreadable] [unreadable] [unreadable]..
  35. Protanoids, Colitis, and Colon Cancer in Gia2-KO mice
    Robert Edwards; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  36. Chemokine Signaling and Colitis in Gia2 Deficient Mice
    Robert Edwards; Fiscal Year: 2006
    ..This application has the support of outstanding mentors at two institutions, and funding of this application will foster Dr Edwards' continued development as a physician-scientist. ..
  37. Gene expression profiles to predict ovarian cancer chemo-response in the elderly
    Johnathan Lancaster; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  38. The Role of Chfr In Tumorigenesis
    Zheng Fu; Fiscal Year: 2007
    ..abstract_text> ..
  39. Diet, Epigenetic Events, And Cancer Prevention
    David Martin; Fiscal Year: 2009
    ..3. Investigate effects of methyl donor supplementation on CpG methylation of the A-vy allele We will use bisulphite allelic sequencing to obtain a detailed picture of the methylation status of the allele in mice bred for Aims 1 and 2. ..
  40. Do Physicians Understand Uncertain Variants and Other Genetic Test Results?
    Sharon Plon; Fiscal Year: 2009
    ..With the increasing availability of complex testing modalities, e.g. DNA and RNA gene chips, for a variety of both rare and common diseases, appropriate reporting and physician education must accompany the development of these tests. ..
  41. Hypomorphic Mismatch Repair Gene Mutations and Single Molecular MSI Analyses
    Steven Lipkin; Fiscal Year: 2007
    ..SPECIFIC AIM 2: To Test Single-Molecule MSI as a Validation Assay for Additional Predicted MLH1/MSH2 deleterious alleles in MSS CRCs. [unreadable] [unreadable] [unreadable]..
  42. MOLECULAR EPIDEMIOLOGY OF COLORECTAL CANCER
    Stephen Gruber; Fiscal Year: 2008
    ..abstract_text> ..
  43. Cytogenetic Analysis of Recombination in the Human Male
    Terry Hassold; Fiscal Year: 2008
    ..abstract_text> ..