beta-Catenin and adenomatous polyposis coli (APC) mutations in adenomas from hereditary non-polyposis colorectal cancer patients

Citation
Y. Akiyama et al., beta-Catenin and adenomatous polyposis coli (APC) mutations in adenomas from hereditary non-polyposis colorectal cancer patients, CANCER LETT, 157(2), 2000, pp. 185-191
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER LETTERS
ISSN journal
0304-3835 → ACNP
Volume
157
Issue
2
Year of publication
2000
Pages
185 - 191
Database
ISI
SICI code
0304-3835(20000901)157:2<185:BAAPC(>2.0.ZU;2-V
Abstract
To clarify the roles of the adenomatous polyposis coli (APC) and beta -cate nin genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesi s, we searched for their mutations in 14 HNPCC adenomas with microsatellite instability (MSI). Seven (50%) adenomas exhibited somatic APC mutations, f ive of which were frameshift mutations and the other two nonsense ones. How ever, the APC mutational spectrum of these adenomas was similar to that of sporadic colorectal tumors. Two adenomas (14.3%) with undetectable APC alte rations showed missense mutations at codon 45 (TCT to TTT or to CCT) in bet a -catenin. The MSI frequency in adenomas with beta -catenin mutations was significantly higher than that with APCones (P < 0.001), indicating that mu tations of <beta>-catenin rather than APC are strongly associated with MSI. These data suggest that adenomas with beta -catenin activating mutations a nd some with APC inactivating mutations may be precursors of HNPCC colorect al cancers. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.