Details

Autor(en) / Beteiligte

• OTTINI, L
• FALCHETTI, M
• D'AMICO, C
• AMOROSI, A
• SAIEVA, C
• MASALA, G
• FRATI, L
• CAMA, A
• PALLI, D
• MARIANI-COSTANTINI, R

Titel

Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype

Ist Teil von

• Oncogene, 1998-05, Vol.16 (21), p.2767-2772

Ort / Verlag

Basingstoke: Nature Publishing

Erscheinungsjahr

1998

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 MSI > or = 3 loci. We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta 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-beta RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats.