Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1997 Jun;105(Suppl 4):775–780. doi: 10.1289/ehp.105-1470030

DNA mismatch repair gene mutations in human cancer.

P Peltomäki 1
PMCID: PMC1470030  PMID: 9255561

Abstract

A new pathogenetic mechanism leading to cancer has been delineated in the past 3 years when human homologues of DNA mismatch repair (MMR) genes have been identified and shown to be involved in various types of cancer. Germline mutations of MMR genes cause susceptibility to a hereditary form of colon cancer, hereditary nonpolyposis colon cancer (HNPCC), which represents one of the most common syndromes associated with cancer predisposition in man. Tumors from HNPCC patients are hypermutable and show length variation at short tandem repeat sequences, a phenomenon referred to as microsatellite instability or replication errors. A similar abnormality is found in a proportion of sporadic tumors of the colorectum as well as a variety of other organs; acquired mutations in MMR genes or other endogenous or exogenous causes may underlie these cases. Genetic and biochemical characterization of the functions of normal and mutated MMR genes elucidates mechanisms of cancer development and provides tools for diagnostic applications.

Full text

PDF
775

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaltonen L. A., Peltomäki P., Leach F. S., Sistonen P., Pylkkänen L., Mecklin J. P., Järvinen H., Powell S. M., Jen J., Hamilton S. R. Clues to the pathogenesis of familial colorectal cancer. Science. 1993 May 7;260(5109):812–816. doi: 10.1126/science.8484121. [DOI] [PubMed] [Google Scholar]
  2. Aaltonen L. A., Peltomäki P., Mecklin J. P., Järvinen H., Jass J. R., Green J. S., Lynch H. T., Watson P., Tallqvist G., Juhola M. Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res. 1994 Apr 1;54(7):1645–1648. [PubMed] [Google Scholar]
  3. Aquilina G., Biondo R., Dogliotti E., Bignami M. Genetic consequences of tolerance to methylation DNA damage in mammalian cells. Carcinogenesis. 1993 Oct;14(10):2097–2103. doi: 10.1093/carcin/14.10.2097. [DOI] [PubMed] [Google Scholar]
  4. Baker S. M., Bronner C. E., Zhang L., Plug A. W., Robatzek M., Warren G., Elliott E. A., Yu J., Ashley T., Arnheim N. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell. 1995 Jul 28;82(2):309–319. doi: 10.1016/0092-8674(95)90318-6. [DOI] [PubMed] [Google Scholar]
  5. Baker S. M., Bronner C. E., Zhang L., Plug A. W., Robatzek M., Warren G., Elliott E. A., Yu J., Ashley T., Arnheim N. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell. 1995 Jul 28;82(2):309–319. doi: 10.1016/0092-8674(95)90318-6. [DOI] [PubMed] [Google Scholar]
  6. Baker S. M., Plug A. W., Prolla T. A., Bronner C. E., Harris A. C., Yao X., Christie D. M., Monell C., Arnheim N., Bradley A. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet. 1996 Jul;13(3):336–342. doi: 10.1038/ng0796-336. [DOI] [PubMed] [Google Scholar]
  7. Bhattacharyya N. P., Skandalis A., Ganesh A., Groden J., Meuth M. Mutator phenotypes in human colorectal carcinoma cell lines. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6319–6323. doi: 10.1073/pnas.91.14.6319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bronner C. E., Baker S. M., Morrison P. T., Warren G., Smith L. G., Lescoe M. K., Kane M., Earabino C., Lipford J., Lindblom A. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994 Mar 17;368(6468):258–261. doi: 10.1038/368258a0. [DOI] [PubMed] [Google Scholar]
  9. Canzian F., Ushijima T., Serikawa T., Wakabayashi K., Sugimura T., Nagao M. Instability of microsatellites in rat colon tumors induced by heterocyclic amines. Cancer Res. 1994 Dec 15;54(24):6315–6317. [PubMed] [Google Scholar]
  10. Cawkwell L., Li D., Lewis F. A., Martin I., Dixon M. F., Quirke P. Microsatellite instability in colorectal cancer: improved assessment using fluorescent polymerase chain reaction. Gastroenterology. 1995 Aug;109(2):465–471. doi: 10.1016/0016-5085(95)90334-8. [DOI] [PubMed] [Google Scholar]
  11. Drummond J. T., Li G. M., Longley M. J., Modrich P. Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells. Science. 1995 Jun 30;268(5219):1909–1912. doi: 10.1126/science.7604264. [DOI] [PubMed] [Google Scholar]
  12. Duggan B. D., Felix J. C., Muderspach L. I., Tourgeman D., Zheng J., Shibata D. Microsatellite instability in sporadic endometrial carcinoma. J Natl Cancer Inst. 1994 Aug 17;86(16):1216–1221. doi: 10.1093/jnci/86.16.1216. [DOI] [PubMed] [Google Scholar]
  13. Fishel R., Ewel A., Lee S., Lescoe M. K., Griffith J. Binding of mismatched microsatellite DNA sequences by the human MSH2 protein. Science. 1994 Nov 25;266(5189):1403–1405. doi: 10.1126/science.7973733. [DOI] [PubMed] [Google Scholar]
  14. Fishel R., Lescoe M. K., Rao M. R., Copeland N. G., Jenkins N. A., Garber J., Kane M., Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993 Dec 3;75(5):1027–1038. doi: 10.1016/0092-8674(93)90546-3. [DOI] [PubMed] [Google Scholar]
  15. Flaman J. M., Frebourg T., Moreau V., Charbonnier F., Martin C., Chappuis P., Sappino A. P., Limacher I. M., Bron L., Benhattar J. A simple p53 functional assay for screening cell lines, blood, and tumors. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3963–3967. doi: 10.1073/pnas.92.9.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fong K. M., Zimmerman P. V., Smith P. J. Microsatellite instability and other molecular abnormalities in non-small cell lung cancer. Cancer Res. 1995 Jan 1;55(1):28–30. [PubMed] [Google Scholar]
  17. Fujii H., Shimada T. Isolation and characterization of cDNA clones derived from the divergently transcribed gene in the region upstream from the human dihydrofolate reductase gene. J Biol Chem. 1989 Jun 15;264(17):10057–10064. [PubMed] [Google Scholar]
  18. Gao X., Wu N., Grignon D., Zacharek A., Liu H., Salkowski A., Li G., Sakr W., Sarkar F., Porter A. T. High frequency of mutator phenotype in human prostatic adenocarcinoma. Oncogene. 1994 Oct;9(10):2999–3003. [PubMed] [Google Scholar]
  19. Gonzalez-Zulueta M., Ruppert J. M., Tokino K., Tsai Y. C., Spruck C. H., 3rd, Miyao N., Nichols P. W., Hermann G. G., Horn T., Steven K. Microsatellite instability in bladder cancer. Cancer Res. 1993 Dec 1;53(23):5620–5623. [PubMed] [Google Scholar]
  20. Han H. J., Yanagisawa A., Kato Y., Park J. G., Nakamura Y. Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer. Cancer Res. 1993 Nov 1;53(21):5087–5089. [PubMed] [Google Scholar]
  21. Hemminki A., Peltomäki P., Mecklin J. P., Järvinen H., Salovaara R., Nyström-Lahti M., de la Chapelle A., Aaltonen L. A. Loss of the wild type MLH1 gene is a feature of hereditary nonpolyposis colorectal cancer. Nat Genet. 1994 Dec;8(4):405–410. doi: 10.1038/ng1294-405. [DOI] [PubMed] [Google Scholar]
  22. Horii A., Han H. J., Sasaki S., Shimada M., Nakamura Y. Cloning, characterization and chromosomal assignment of the human genes homologous to yeast PMS1, a member of mismatch repair genes. Biochem Biophys Res Commun. 1994 Nov 15;204(3):1257–1264. doi: 10.1006/bbrc.1994.2598. [DOI] [PubMed] [Google Scholar]
  23. Ionov Y., Peinado M. A., Malkhosyan S., Shibata D., Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993 Jun 10;363(6429):558–561. doi: 10.1038/363558a0. [DOI] [PubMed] [Google Scholar]
  24. Lazar V., Grandjouan S., Bognel C., Couturier D., Rougier P., Bellet D., Bressac-de Paillerets B. Accumulation of multiple mutations in tumour suppressor genes during colorectal tumorigenesis in HNPCC patients. Hum Mol Genet. 1994 Dec;3(12):2257–2260. doi: 10.1093/hmg/3.12.2257. [DOI] [PubMed] [Google Scholar]
  25. Leach F. S., Nicolaides N. C., Papadopoulos N., Liu B., Jen J., Parsons R., Peltomäki P., Sistonen P., Aaltonen L. A., Nyström-Lahti M. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993 Dec 17;75(6):1215–1225. doi: 10.1016/0092-8674(93)90330-s. [DOI] [PubMed] [Google Scholar]
  26. Levinson G., Gutman G. A. High frequencies of short frameshifts in poly-CA/TG tandem repeats borne by bacteriophage M13 in Escherichia coli K-12. Nucleic Acids Res. 1987 Jul 10;15(13):5323–5338. doi: 10.1093/nar/15.13.5323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Liu B., Nicolaides N. C., Markowitz S., Willson J. K., Parsons R. E., Jen J., Papadopolous N., Peltomäki P., de la Chapelle A., Hamilton S. R. Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nat Genet. 1995 Jan;9(1):48–55. doi: 10.1038/ng0195-48. [DOI] [PubMed] [Google Scholar]
  28. Liu B., Parsons R., Papadopoulos N., Nicolaides N. C., Lynch H. T., Watson P., Jass J. R., Dunlop M., Wyllie A., Peltomäki P. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med. 1996 Feb;2(2):169–174. doi: 10.1038/nm0296-169. [DOI] [PubMed] [Google Scholar]
  29. Loeb L. A. Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Res. 1994 Oct 1;54(19):5059–5063. [PubMed] [Google Scholar]
  30. Lothe R. A., Peltomäki P., Meling G. I., Aaltonen L. A., Nyström-Lahti M., Pylkkänen L., Heimdal K., Andersen T. I., Møller P., Rognum T. O. Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res. 1993 Dec 15;53(24):5849–5852. [PubMed] [Google Scholar]
  31. Luce M. C., Marra G., Chauhan D. P., Laghi L., Carethers J. M., Cherian S. P., Hawn M., Binnie C. G., Kam-Morgan L. N., Cayouette M. C. In vitro transcription/translation assay for the screening of hMLH1 and hMSH2 mutations in familial colon cancer. Gastroenterology. 1995 Oct;109(4):1368–1374. doi: 10.1016/0016-5085(95)90600-2. [DOI] [PubMed] [Google Scholar]
  32. Lynch H. T., Smyrk T. C., Watson P., Lanspa S. J., Lynch J. F., Lynch P. M., Cavalieri R. J., Boland C. R. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology. 1993 May;104(5):1535–1549. doi: 10.1016/0016-5085(93)90368-m. [DOI] [PubMed] [Google Scholar]
  33. MacPhee D. G. Mismatch repair, somatic mutations, and the origins of cancer. Cancer Res. 1995 Dec 1;55(23):5489–5492. [PubMed] [Google Scholar]
  34. Mao L., Lee D. J., Tockman M. S., Erozan Y. S., Askin F., Sidransky D. Microsatellite alterations as clonal markers for the detection of human cancer. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9871–9875. doi: 10.1073/pnas.91.21.9871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Meltzer S. J., Yin J., Manin B., Rhyu M. G., Cottrell J., Hudson E., Redd J. L., Krasna M. J., Abraham J. M., Reid B. J. Microsatellite instability occurs frequently and in both diploid and aneuploid cell populations of Barrett's-associated esophageal adenocarcinomas. Cancer Res. 1994 Jul 1;54(13):3379–3382. [PubMed] [Google Scholar]
  36. Merlo A., Mabry M., Gabrielson E., Vollmer R., Baylin S. B., Sidransky D. Frequent microsatellite instability in primary small cell lung cancer. Cancer Res. 1994 Apr 15;54(8):2098–2101. [PubMed] [Google Scholar]
  37. Modrich P. Mechanisms and biological effects of mismatch repair. Annu Rev Genet. 1991;25:229–253. doi: 10.1146/annurev.ge.25.120191.001305. [DOI] [PubMed] [Google Scholar]
  38. Modrich P. Mismatch repair, genetic stability, and cancer. Science. 1994 Dec 23;266(5193):1959–1960. doi: 10.1126/science.7801122. [DOI] [PubMed] [Google Scholar]
  39. Murty V. V., Li R. G., Mathew S., Reuter V. E., Bronson D. L., Bosl G. J., Chaganti R. S. Replication error-type genetic instability at 1q42-43 in human male germ cell tumors. Cancer Res. 1994 Aug 1;54(15):3983–3985. [PubMed] [Google Scholar]
  40. Myeroff L. L., Parsons R., Kim S. J., Hedrick L., Cho K. R., Orth K., Mathis M., Kinzler K. W., Lutterbaugh J., Park K. A transforming growth factor beta receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. Cancer Res. 1995 Dec 1;55(23):5545–5547. [PubMed] [Google Scholar]
  41. Nicolaides N. C., Carter K. C., Shell B. K., Papadopoulos N., Vogelstein B., Kinzler K. W. Genomic organization of the human PMS2 gene family. Genomics. 1995 Nov 20;30(2):195–206. doi: 10.1006/geno.1995.9885. [DOI] [PubMed] [Google Scholar]
  42. Nicolaides N. C., Papadopoulos N., Liu B., Wei Y. F., Carter K. C., Ruben S. M., Rosen C. A., Haseltine W. A., Fleischmann R. D., Fraser C. M. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994 Sep 1;371(6492):75–80. doi: 10.1038/371075a0. [DOI] [PubMed] [Google Scholar]
  43. Nyström-Lahti M., Wu Y., Moisio A. L., Hofstra R. M., Osinga J., Mecklin J. P., Järvinen H. J., Leisti J., Buys C. H., de la Chapelle A. DNA mismatch repair gene mutations in 55 kindreds with verified or putative hereditary non-polyposis colorectal cancer. Hum Mol Genet. 1996 Jun;5(6):763–769. doi: 10.1093/hmg/5.6.763. [DOI] [PubMed] [Google Scholar]
  44. Orlow I., Lianes P., Lacombe L., Dalbagni G., Reuter V. E., Cordon-Cardo C. Chromosome 9 allelic losses and microsatellite alterations in human bladder tumors. Cancer Res. 1994 Jun 1;54(11):2848–2851. [PubMed] [Google Scholar]
  45. Palombo F., Gallinari P., Iaccarino I., Lettieri T., Hughes M., D'Arrigo A., Truong O., Hsuan J. J., Jiricny J. GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells. Science. 1995 Jun 30;268(5219):1912–1914. doi: 10.1126/science.7604265. [DOI] [PubMed] [Google Scholar]
  46. Papadopoulos N., Leach F. S., Kinzler K. W., Vogelstein B. Monoallelic mutation analysis (MAMA) for identifying germline mutations. Nat Genet. 1995 Sep;11(1):99–102. doi: 10.1038/ng0995-99. [DOI] [PubMed] [Google Scholar]
  47. Papadopoulos N., Nicolaides N. C., Liu B., Parsons R., Lengauer C., Palombo F., D'Arrigo A., Markowitz S., Willson J. K., Kinzler K. W. Mutations of GTBP in genetically unstable cells. Science. 1995 Jun 30;268(5219):1915–1917. doi: 10.1126/science.7604266. [DOI] [PubMed] [Google Scholar]
  48. Parsons R., Li G. M., Longley M. J., Fang W. H., Papadopoulos N., Jen J., de la Chapelle A., Kinzler K. W., Vogelstein B., Modrich P. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993 Dec 17;75(6):1227–1236. doi: 10.1016/0092-8674(93)90331-j. [DOI] [PubMed] [Google Scholar]
  49. Parsons R., Li G. M., Longley M., Modrich P., Liu B., Berk T., Hamilton S. R., Kinzler K. W., Vogelstein B. Mismatch repair deficiency in phenotypically normal human cells. Science. 1995 May 5;268(5211):738–740. doi: 10.1126/science.7632227. [DOI] [PubMed] [Google Scholar]
  50. Peltomäki P., Aaltonen L. A., Sistonen P., Pylkkänen L., Mecklin J. P., Järvinen H., Green J. S., Jass J. R., Weber J. L., Leach F. S. Genetic mapping of a locus predisposing to human colorectal cancer. Science. 1993 May 7;260(5109):810–812. doi: 10.1126/science.8484120. [DOI] [PubMed] [Google Scholar]
  51. Peltomäki P., Lothe R. A., Aaltonen L. A., Pylkkänen L., Nyström-Lahti M., Seruca R., David L., Holm R., Ryberg D., Haugen A. Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome. Cancer Res. 1993 Dec 15;53(24):5853–5855. [PubMed] [Google Scholar]
  52. Prolla T. A., Pang Q., Alani E., Kolodner R. D., Liskay R. M. MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science. 1994 Aug 19;265(5175):1091–1093. doi: 10.1126/science.8066446. [DOI] [PubMed] [Google Scholar]
  53. Reitmair A. H., Schmits R., Ewel A., Bapat B., Redston M., Mitri A., Waterhouse P., Mittrücker H. W., Wakeham A., Liu B. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet. 1995 Sep;11(1):64–70. doi: 10.1038/ng0995-64. [DOI] [PubMed] [Google Scholar]
  54. Renan M. J. How many mutations are required for tumorigenesis? Implications from human cancer data. Mol Carcinog. 1993;7(3):139–146. doi: 10.1002/mc.2940070303. [DOI] [PubMed] [Google Scholar]
  55. Rhyu M. G., Park W. S., Meltzer S. J. Microsatellite instability occurs frequently in human gastric carcinoma. Oncogene. 1994 Jan;9(1):29–32. [PubMed] [Google Scholar]
  56. Risinger J. I., Berchuck A., Kohler M. F., Watson P., Lynch H. T., Boyd J. Genetic instability of microsatellites in endometrial carcinoma. Cancer Res. 1993 Nov 1;53(21):5100–5103. [PubMed] [Google Scholar]
  57. Ryberg D., Lindstedt B. A., Zienolddiny S., Haugen A. A hereditary genetic marker closely associated with microsatellite instability in lung cancer. Cancer Res. 1995 Sep 15;55(18):3996–3999. [PubMed] [Google Scholar]
  58. Sancar A. Mechanisms of DNA excision repair. Science. 1994 Dec 23;266(5193):1954–1956. doi: 10.1126/science.7801120. [DOI] [PubMed] [Google Scholar]
  59. Seruca R., Santos N. R., David L., Constância M., Barroca H., Carneiro F., Seixas M., Peltomäki P., Lothe R., Sobrinho-Simões M. Sporadic gastric carcinomas with microsatellite instability display a particular clinicopathologic profile. Int J Cancer. 1995 Feb 20;64(1):32–36. doi: 10.1002/ijc.2910640108. [DOI] [PubMed] [Google Scholar]
  60. Shibata D., Peinado M. A., Ionov Y., Malkhosyan S., Perucho M. Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nat Genet. 1994 Mar;6(3):273–281. doi: 10.1038/ng0394-273. [DOI] [PubMed] [Google Scholar]
  61. Shridhar V., Siegfried J., Hunt J., del Mar Alonso M., Smith D. I. Genetic instability of microsatellite sequences in many non-small cell lung carcinomas. Cancer Res. 1994 Apr 15;54(8):2084–2087. [PubMed] [Google Scholar]
  62. Strand M., Earley M. C., Crouse G. F., Petes T. D. Mutations in the MSH3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10418–10421. doi: 10.1073/pnas.92.22.10418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Strand M., Prolla T. A., Liskay R. M., Petes T. D. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature. 1993 Sep 16;365(6443):274–276. doi: 10.1038/365274a0. [DOI] [PubMed] [Google Scholar]
  64. Thibodeau S. N., Bren G., Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993 May 7;260(5109):816–819. doi: 10.1126/science.8484122. [DOI] [PubMed] [Google Scholar]
  65. Thomas D. C., Roberts J. D., Kunkel T. A. Heteroduplex repair in extracts of human HeLa cells. J Biol Chem. 1991 Feb 25;266(6):3744–3751. [PubMed] [Google Scholar]
  66. Uchida T., Wada C., Wang C., Egawa S., Ohtani H., Koshiba K. Genomic instability of microsatellite repeats and mutations of H-, K-, and N-ras, and p53 genes in renal cell carcinoma. Cancer Res. 1994 Jul 15;54(14):3682–3685. [PubMed] [Google Scholar]
  67. Umar A., Boyer J. C., Kunkel T. A. DNA loop repair by human cell extracts. Science. 1994 Nov 4;266(5186):814–816. doi: 10.1126/science.7973637. [DOI] [PubMed] [Google Scholar]
  68. Umar A., Boyer J. C., Thomas D. C., Nguyen D. C., Risinger J. I., Boyd J., Ionov Y., Perucho M., Kunkel T. A. Defective mismatch repair in extracts of colorectal and endometrial cancer cell lines exhibiting microsatellite instability. J Biol Chem. 1994 May 20;269(20):14367–14370. [PubMed] [Google Scholar]
  69. Varlet I., Pallard C., Radman M., Moreau J., de Wind N. Cloning and expression of the Xenopus and mouse Msh2 DNA mismatch repair genes. Nucleic Acids Res. 1994 Dec 25;22(25):5723–5728. doi: 10.1093/nar/22.25.5723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wada C., Shionoya S., Fujino Y., Tokuhiro H., Akahoshi T., Uchida T., Ohtani H. Genomic instability of microsatellite repeats and its association with the evolution of chronic myelogenous leukemia. Blood. 1994 Jun 15;83(12):3449–3456. [PubMed] [Google Scholar]
  71. Weber C. A., Salazar E. P., Stewart S. A., Thompson L. H. ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3. EMBO J. 1990 May;9(5):1437–1447. doi: 10.1002/j.1460-2075.1990.tb08260.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
  73. Wijnen J., Vasen H., Khan P. M., Menko F. H., van der Klift H., van Leeuwen C., van den Broek M., van Leeuwen-Cornelisse I., Nagengast F., Meijers-Heijboer A. Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing gradient-gel electrophoresis. Am J Hum Genet. 1995 May;56(5):1060–1066. [PMC free article] [PubMed] [Google Scholar]
  74. Wooster R., Cleton-Jansen A. M., Collins N., Mangion J., Cornelis R. S., Cooper C. S., Gusterson B. A., Ponder B. A., von Deimling A., Wiestler O. D. Instability of short tandem repeats (microsatellites) in human cancers. Nat Genet. 1994 Feb;6(2):152–156. doi: 10.1038/ng0294-152. [DOI] [PubMed] [Google Scholar]
  75. Yee C. J., Roodi N., Verrier C. S., Parl F. F. Microsatellite instability and loss of heterozygosity in breast cancer. Cancer Res. 1994 Apr 1;54(7):1641–1644. [PubMed] [Google Scholar]
  76. de Wind N., Dekker M., Berns A., Radman M., te Riele H. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell. 1995 Jul 28;82(2):321–330. doi: 10.1016/0092-8674(95)90319-4. [DOI] [PubMed] [Google Scholar]
  77. de la Chapelle A., Peltomäki P. Genetics of hereditary colon cancer. Annu Rev Genet. 1995;29:329–348. doi: 10.1146/annurev.ge.29.120195.001553. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES