Mutational analysis of MLH1 and MSH2 in 25 prospectively-acquired RER+ endometrial cancers. Genes Chromosomes Cancer 1997 Mar;18(3):219-27
Date
03/01/1997Pubmed ID
9071575DOI
10.1002/(sici)1098-2264(199703)18:3<219::aid-gcc8>3.0.co;2-4Scopus ID
2-s2.0-0030997158 (requires institutional sign-in at Scopus site) 108 CitationsAbstract
Mutations in the DNA mismatch repair (MMR) genes MLH1 and MSH2 have been linked to several human cancers which display the replication error (RER) phenotype. Germline mutations in these two genes have been implicated in about 90% of families with hereditary nonpolyposis colorectal cancer (HNPCC). A significant proportion of endometrial cancers, the second most common malignancy of the HNPCC syndrome, also exhibit RER. We screened 125 primary endometrial adenocarcinomas with seven microsatellite markers and identified 25 specimens with RER (20%). We used single-strand conformation variant analysis to search for mutations in MLH1 and MSH2. Direct sequencing of variants revealed only one germline mutation in MLH1 and a single somatic mutation in MSH2. However, six previously unreported sequence polymorphisms in MLH1 were identified. Four of these polymorphisms show clear population-based differences in allele frequency. In addition, a highly informative marker for MLH1 was characterized. The low frequency of mutations in MLH1 and MSH2 in this large series of cancers suggests that other MMR genes are responsible for the RER phenotype in endometrial cancers.
Author List
Kowalski LD, Mutch DG, Herzog TJ, Rader JS, Goodfellow PJAuthor
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAdult
Aged
Aged, 80 and over
Carcinoma
Carrier Proteins
DNA Mutational Analysis
DNA Repair
DNA Replication
DNA, Neoplasm
DNA-Binding Proteins
Endometrial Neoplasms
Female
Gene Frequency
Genetic Markers
Humans
Middle Aged
MutL Protein Homolog 1
MutS Homolog 2 Protein
Mutation
Neoplasm Proteins
Nuclear Proteins
Polymorphism, Genetic
Polymorphism, Single-Stranded Conformational
Proto-Oncogene Proteins
