title: Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype.
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 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.
authors.affiliation: Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ottini
authors.forename: M
authors.initials: M
authors.lastname: Falchetti
authors.forename: C
authors.initials: C
authors.lastname: D'Amico
authors.forename: A
authors.initials: A
authors.lastname: Amorosi
authors.forename: C
authors.initials: C
authors.lastname: Saieva
authors.forename: G
authors.initials: G
authors.lastname: Masala
authors.forename: L
authors.initials: L
authors.lastname: Frati
authors.forename: A
authors.initials: A
authors.lastname: Cama
authors.forename: D
authors.initials: D
authors.lastname: Palli
authors.forename: R
authors.initials: R
authors.lastname: Mariani-Costantini
mesh_terms: D000368:Aged; D024682:BRCA2 Protein; D015820:Cadherins / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D051028:bcl-2-Associated X Protein
chemical_list: D024682:BRCA2 Protein; D015820:Cadherins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C094443:G-T mismatch-binding protein; C078444:MSH3 protein, human; C421109:multidrug resistance-associated protein 1