RGD Reference Report - Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair. - Rat Genome Database

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Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair.

Authors: Risinger, JI  Umar, A  Boyd, J  Berchuck, A  Kunkel, TA  Barrett, JC 
Citation: Risinger JI, etal., Nat Genet. 1996 Sep;14(1):102-5.
RGD ID: 1600456
Pubmed: PMID:8782829   (View Abstract at PubMed)
DOI: DOI:10.1038/ng0996-102   (Journal Full-text)

Many human tumours have length alterations in repetitive sequence elements. Although this microsatellite instability has been attributed to mutations in four DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds, many sporadic tumours exhibit instability but no detectable mutations in these genes. It is therefore of interest to identify other genes that contribute to this instability. In yeast, mutations in several genes, including RTH and MSH3, cause microsatellite instability. Thus, we screened 16 endometrial carcinomas with microsatellite instability for alterations in FEN1 (the human homolog of RTH) and in MSH3 (refs 12-14). Although we found no FEN1 mutations, a frameshift mutation in MSH3 was observed in an endometrial carcinoma and in an endometrial carcinoma cell line. Extracts of the cell line were deficient in repair of DNA substrates containing mismatches or extra nucleotides. Introducing chromosome 5, encoding the MSH3 gene, into the mutant cell line increased the stability of some but not all microsatellites. Extracts of these cells repaired certain substrates containing extra nucleotides, but were deficient in repair of those containing mismatches or other extra nucleotides. A subsequent search revealed a second gene mutation in HHUA cells, a missense mutation in the MSH6 gene. Together the data suggest that the MSH3 gene encodes a product that functions in repair of some but not all pre-mutational intermediates, its mutation in tumours can result in genomic instability and, as in yeast, MSH3 and MSH6 are partially redundant for mismatch repair.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endometrial carcinoma  IAGP 1600456 RGD 
endometrial carcinoma  ISOMSH3 (Homo sapiens)1600456; 1600456 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Msh3  (mutS homolog 3)

Genes (Mus musculus)
Msh3  (mutS homolog 3)

Genes (Homo sapiens)
MSH3  (mutS homolog 3)


Additional Information