TY - JOUR
T1 - Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype
AU - Ottini, Laura
AU - Falchetti, Mario
AU - D'Amico, Cristina
AU - Amorosi, Andrea
AU - Saieva, Calogero
AU - Masala, Giovanna
AU - Frati, Luigi
AU - Cama, Alessandro
AU - Palli, Domenico
AU - Mariani-Costantini, Renato
PY - 1998/5/28
Y1 - 1998/5/28
N2 - 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 MS ≤ 3 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 in 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.
AB - 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 MS ≤ 3 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 in 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.
KW - BAX
KW - BRCA2
KW - Gastric cancer
KW - hMSH3
KW - hMSH6
KW - IGFIIR
KW - Microsatellite instability
KW - Mutation
KW - TGFβ-RII
UR - http://www.scopus.com/inward/record.url?scp=7144253787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7144253787&partnerID=8YFLogxK
M3 - Article
C2 - 9652743
AN - SCOPUS:7144253787
VL - 16
SP - 2767
EP - 2772
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 21
ER -