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• W2037221522 abstract "Loss of genome stability is a feature of cancer cells [ 1 Lengauer C. Kinzler K.W. Vogelstein B. Genetic instabilites in human cancers. Nature. 1998; 396: 643-649 Crossref PubMed Scopus (3415) Google Scholar , 2 Hanahan D. Weinberg R.A. The hallmarks of cancer. Cell. 2000; 100: 57-70 Abstract Full Text Full Text PDF PubMed Scopus (22805) Google Scholar ]. The molecular and clinical progression of tumors depends on failures in normal DNA repair processes. The notion that tumor cells are hypermutable (have a so-called mutator phenotype) was first put forth by Loeb in 1991 [ [3] Loeb L.A. Mutator phenotype may be required for multistage carcinogenesis. Cancer. Research. 1991; 51: 3075-3079 PubMed Google Scholar ] and loss of DNA mismatch repair (DMMR) was first described in human tumors in 1993 [ 4 Thibodeau S.N. Bren G. Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993; 260: 816-819 Crossref PubMed Scopus (2819) Google Scholar , 5 Aaltonen L.A. Peltomaki P. Leach F.S. Sistonen P. Pylkkanen L. Mecklin J.P. et al. Clues to the pathogenesis of familial colorectal cancer. Science. 1993; 260: 812-815 Crossref PubMed Scopus (2586) Google Scholar , 6 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; 363: 558-561 Crossref PubMed Scopus (2427) Google Scholar , 7 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; 53: 5100-5103 PubMed Google Scholar ]. Naturally occurring strand slippage mutations in short repetitive elements go unrecognized in tumor cells that lack DMMR. The consequence is the accumulation of insertion and deletion mutations that are products of replication errors. Tumors with these sorts of abnormalities in repetitive DNA sequences have been referred to as RER-positive (replication error-positive). The DNA sequences most subject to strand slippage mutations are called microsatellites, and consequently the tumor abnormality that is detected is also referred to as microsatellite instability (MSI). Tumor cells lacking DNA mismatch repair accumulate mutations at a much higher rate than those with an intact mismatch repair system. Endometrial cancers frequently have defects in DNA mismatch repair with ∼25% of all endometrial cancers exhibiting the tumor DNA MSI-positive phenotype. The remaining 75% of tumors are referred to as microsatellite stable (MSS)." @default.
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• W2037221522 date "2009-05-01" @default.
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• W2037221522 title "Clinicopathologic significance of DNA mismatch repair defects in endometrial cancer: The devil is in the details" @default.
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• W2037221522 doi "https://doi.org/10.1016/j.ygyno.2009.03.013" @default.
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