Alterations of repeated sequences in 5 ' upstream and coding regions in colorectal tumors from patients with hereditary nonpolyposis colorectal cancer and Turcot syndrome

Citation
M. Miyaki et al., Alterations of repeated sequences in 5 ' upstream and coding regions in colorectal tumors from patients with hereditary nonpolyposis colorectal cancer and Turcot syndrome, ONCOGENE, 20(37), 2001, pp. 5215-5218
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
20
Issue
37
Year of publication
2001
Pages
5215 - 5218
Database
ISI
SICI code
0950-9232(20010823)20:37<5215:AORSI5>2.0.ZU;2-3
Abstract
One of the characteristics of tumors from patients with germline mutations of DNA mismatch repair genes is instability at microsatellite regions (MSI) . We analysed alterations at repeated sequences of coding regions, as well as those of 5' upstream regions, in 29 MSI-High colorectal tumors from pati ents with hereditary nonpolyposis colorectal cancer (HNPCC) and Turcot synd rome. We found that repeated sequences in 5' upstream regions were altered in these tumors, at considerable frequencies. The (A)(10) repeat in the pro moter region (position - 178 similar to - 169) of the GAPDH gene was altere d in 17% of the tumors. The (A)(10)(TA)(9) in the 5' upstream region (posit ion -318 similar to -291) of the mitochondrial isoleucyl tRNA synthetase ge ne (IIeRS-A), coded in nuclear DNA, was altered in 59% of the tumors, where as (A)(9) in the 5' upstream region (position -859 similar to -851) of cyto plasmic isoleucyl tRNA synthetase gene (IIeRS-B) was not altered. Alteratio n at repeated sequences in the coding regions were 72% at TGF beta RII(A)(1 0), 24% at IGFIIR(G)(8), 45% at BAX(G)(8), 55% at E2F4(CAG)(13), 66% at cas pase-5 (A)(10), 31% at MBD4(A)(10), 55% at hMSH3(A)(8) and 34% at hMSH6(C)( 8). The number of altered genes increased with the advancement of carcinoma according to Dukes categories: mean numbers of altered genes within these 10 genes were 2.6 for Dukes A, 4.7 for Dukes B and 7.8 for Dukes C. The mea n number for adenomas was 2.0. These results suggest that the MSI phenotype also causes alteration of 5' upstream regions which may affect apoptosis a nd some mitochondrial functions in HNPCC and Turcot tumors, and that accumu lation of altered genes with repeated sequences is associated with the prog ression of HNPCC and Turcot colorectal tumors.