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- Title
Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype.
- Authors
Ottini, Laura; Falchetti, Mario; D'Amico, Cristina; Amorosi, Andrea; Saieva, Calogero; Masala, Giovanna; Frati, Luigi; Cama, Alessandro; Palli, Domenico; Mariani-Costantini, Renato
- Abstract
We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI). The tumors included: ten cases with no MSI, 14 cases with MSI=1 locus, 13 cases with MSI=two loci and 13 cases with MSI3 loci. We investigated coding repeats within the TGF-β RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-β RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to hMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3′ UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-β RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats.
- Subjects
GASTROINTESTINAL cancer; GENETIC mutation; MICROSATELLITE repeats
- Publication
Oncogene, 1998, Vol 16, Issue 21, p2767
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1201816