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Mutations in MLH1 are more frequent than in MSH2 in sporadic colorectal cancers with microsatellite instability
Author(s) -
Herfarth Klaus K.F.,
Kodner Ira J.,
Whelan Alison J.,
Ivanovich Jennifer L.,
Bracamontes John R.,
Wells Samuel A.,
Goodfellow Paul J.
Publication year - 1997
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199701)18:1<42::aid-gcc5>3.0.co;2-1
Subject(s) - mlh1 , microsatellite instability , msh2 , germline mutation , dna mismatch repair , biology , cancer research , mutation , colorectal cancer , genetics , microsatellite , genome instability , cancer , gene , dna , dna damage , allele
The microsatellite instability that is a feature of tumors in patients with hereditary nonpolyposis colorectal cancer (HNPCC) is a consequence of defective DNA mismatch repair. Mutations in the DNA mismatch repair genes MSH2 and MLH1 may account for up to 90% of HNPCC kindreds. Microsatellite instability is also seen in 10–16% of sporadic colorectal cancers. A limited number of MSH2 and MLH1 mutations have been described for sporadic colorectal cancers. In this study, we screened 12 primary sporadic colorectal cancers with microsatellite instability for mutations in MSH2 and MLH1 by using reverse transcription‐polymerase chain reaction (RT‐PCR) and single‐strand‐conformation‐variant (SSCV) analysis. Eight mutations were identified in six tumors. One mutation in MLH1 was found to be present in the patient's germline DNA. Four tumors had somatic mutations in MLH1 , and, in two of these tumors, two different mutations were identified. A single tumor had a somatic MSH2 mutation. Our observations suggest that MLH1 is mutated more frequently than MSH2 in sporadic colorectal cancers with microsatellite instability. Genes Chromosom. Cancer 18:42–49, 1997 . © 1997 Wiley‐Liss, Inc.