Cancer in Predisposing to Colorectal hPMS 2 and hPMS 1 The Role of Updated Version

Hereditary nonpolyposis colorectal cancer (HNPCC) is attributable to a deficiency of mismatch repair. Inactivation of DNA mismatch repair underlies the genesis of microsatellite instability in colorectal cancer. Germline mutations in three DNA mismatch repair genes, hMSH2, hMLH1, and hMSH6, have been found to segregate in HNPCC and HNPCC-like families. The two DNA mismatch repair genes hPMS1 and hPMS2 have also been suggested to predispose to HNPCC. In this study, 84 HNPCC and HNPCC-like kindreds without known mutations in the other three known DNA mismatch repair genes were screened for germline mutations in the hPMS1 or hPMS2 gene. No clear-cut pathogenic mutations were identified. Conversion technology was used to detect a large hMSH2 deletion in two affected members of the kindred in which the hPMS1 mutation was originally reported, whereas the hPMS1 mutation was only present in one of these two individuals. Since the hPMS1 and hPMS2 genes were first reported, germline mutations in hPMS2 have been demonstrated primarily in patients with Turcot’s syndrome. However, no mutation in any of the two genes has been found to segregate in HNPCC families. Until there is better evidence for an increased colorectal cancer risk associated with germline mutations in these genes, a conservative interpretation of the role of mutations in these genes is advised.

[1]  A. Ziogas,et al.  Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases. , 2001, Journal of the National Cancer Institute.

[2]  H. Grönberg,et al.  MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon cancer. , 2001, Cancer research.

[3]  P. Glazer,et al.  Mutagenesis in PMS2- and MSH2-deficient mice indicates differential protection from transversions and frameshifts. , 2000, Carcinogenesis.

[4]  F. Jirik,et al.  Tumors arising in DNA mismatch repair-deficient mice show a wide variation in mutation frequency as assessed by a transgenic reporter gene. , 2000, Carcinogenesis.

[5]  L. Kasturi,et al.  Somatic mutation of hPMS2 as a possible cause of sporadic human colon cancer with microsatellite instability , 2000, Oncogene.

[6]  A. Iannelli,et al.  Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene , 2000, Oncogene.

[7]  James R. Eshleman,et al.  Conversion of diploidy to haploidy , 2000, Nature.

[8]  B. Harfe,et al.  Discrete in vivo roles for the MutL homologs Mlh2p and Mlh3p in the removal of frameshift intermediates in budding yeast , 2000, Current Biology.

[9]  T. Liu,et al.  Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer , 2000, Genes, chromosomes & cancer.

[10]  N. Kleckner,et al.  Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Josef Jiricny,et al.  Identification of hMutLβ, a Heterodimer of hMLH1 and hPMS1* , 1999, The Journal of Biological Chemistry.

[12]  J. Tytell,et al.  Germ-line msh6 mutations in colorectal cancer families. , 1999, Cancer research.

[13]  P. Møller,et al.  Familial endometrial cancer in female carriers of MSH6 germline mutations , 1999, Nature Genetics.

[14]  R. Kucherlapati,et al.  Mouse models for colorectal cancer , 1999, Oncogene.

[15]  J. Saurin,et al.  Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer , 1999, Human Genetics.

[16]  H T Lynch,et al.  New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. , 1999, Gastroenterology.

[17]  G. Hirst,et al.  Dependence on RAD52 and RAD1 for anticancer drug resistance mediated by inactivation of mismatch repair genes , 1999, Current Biology.

[18]  S Srivastava,et al.  A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. , 1998, Cancer research.

[19]  A. Viel,et al.  Lack of PMS2 gene-truncating mutations in patients with hereditary colorectal cancer. , 1998, International journal of oncology.

[20]  T. Kunkel,et al.  Single gene complementation of the hPMS2 defect in HEC-1-A endometrial carcinoma cells. , 1998, Cancer research.

[21]  Darryl Shibata,et al.  Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DMA mismatch repair , 1998, Nature Genetics.

[22]  H. Grönberg,et al.  DGGE screening of mutations in mismatch repair genes (hMSH2 and hMLH1) in 34 Swedish families with colorectal cancer , 1998, Clinical genetics.

[23]  M. Koike,et al.  Drastic genetic instability of tumors and normal tissues in Turcot syndrome , 1997, Oncogene.

[24]  M. Koike,et al.  Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer , 1997, Nature Genetics.

[25]  A. Lindblom,et al.  Tumorigenesis in colorectal tumors from patients with hereditary non-polyposis colorectal cancer , 1997, Human Genetics.

[26]  Y. Yuasa,et al.  Germ-line mutation of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred. , 1997, Cancer research.

[27]  A. Lindblom,et al.  Low frequency of hMSH2 mutations in Swedish HNPCC families , 1997, International journal of cancer.

[28]  G. Thomas,et al.  BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines. , 1997, Cancer research.

[29]  A. Viel,et al.  Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer , 1997, Genes, chromosomes & cancer.

[30]  K. Kinzler,et al.  Analysis of mismatch repair genes in hereditary non–polyposis colorectal cancer patients , 1996, Nature Medicine.

[31]  T. Shimada,et al.  Genomic organization and expression of the human MSH3 gene. , 1996, Genomics.

[32]  A. Lindblom,et al.  Mutation screening in the hMLH1 gene in Swedish hereditary nonpolyposis colon cancer families. , 1995, Cancer research.

[33]  K. Kinzler,et al.  The molecular basis of Turcot's syndrome. , 1995, The New England journal of medicine.

[34]  R. Fleischmann,et al.  Mutations of two P/WS homologues in hereditary nonpolyposis colon cancer , 1994, Nature.

[35]  Russell Higuchi,et al.  Effective amplification of long targets from cloned inserts and human genomic DNA. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[36]  R. Fleischmann,et al.  Mutation of a mutL homolog in hereditary colon cancer. , 1994, Science.

[37]  D. Ward,et al.  Mutation in the DNA mismatch repair gene homologue hMLH 1 is associated with hereditary non-polyposis colon cancer , 1994, Nature.

[38]  Robin J. Leach,et al.  Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer , 1993, Cell.

[39]  K. Kinzler,et al.  Clues to the pathogenesis of familial colorectal cancer. , 1993, Science.

[40]  Andreas D. Baxevanis,et al.  MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability , 2000, Nature Genetics.

[41]  A. Lindblom,et al.  Various mutation screening techniques in the DNA mismatch repair genes hMSH2 and hMLH1. , 1999, Genetic testing.

[42]  H. Lynch,et al.  GENETIC SUSCEPTIBILITY TO NONPOLYPOSIS COLORECTAL CANCER , 1999 .

[43]  A. Viel,et al.  Characterization of MLH1 and MSH2 alternative splicing and its relevance to molecular testing of colorectal cancer susceptibility , 1998, Human Genetics.

[44]  S. Powell,et al.  Mutation of hMSH3 and hMSH6 mismatch repair genes in genetically unstable human colorectal and gastric carcinomas , 1997, Human mutation.