Somatic mutations of the APC, KRAS, and TP53 genes in nonpolypoid colorectal adenomas

Citation
R. Van Wyk et al., Somatic mutations of the APC, KRAS, and TP53 genes in nonpolypoid colorectal adenomas, GENE CHROM, 27(2), 2000, pp. 202-208
Citations number
35
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
GENES CHROMOSOMES & CANCER
ISSN journal
10452257 → ACNP
Volume
27
Issue
2
Year of publication
2000
Pages
202 - 208
Database
ISI
SICI code
1045-2257(200002)27:2<202:SMOTAK>2.0.ZU;2-9
Abstract
Calorectal adenomas are macroscopically visible morphological changes of th e mucosa that can develop focal carcinoma in the absence of surgical interv ention. The successive molecular changes proposed to occur at different: st ages in the adenoma-carcinoma sequence were primarily based on DNA studies of exophytic; polypoid-type adenomas. Nor all colorectal lesions, however, display an exophytic phenotype and a presumed distinct colorectal neoplasm, the nonpolypoid adenoma, was subsequently described as a precursor of colo rectal cancer. The low incidence of KRAS mutations in nonpolypoid colorecta l adenomas reported previously suggested a different genetic basis for the transformation process in these lesions. We have pursued the identification of genetic changes in benign sporadic nanpolypoid colorectal adenomas in a selected Swedish patient group with no family history of colarectal cancer . Mutation screening of the adenomarous polyposis coli (APC), KRAS, and TP5 3 genes was conducted using the protein truncation test, hereroduplex-singl e-strand conformation polymorphism analysis, and denaturing gradient: gel e lectrophoresis on PCR-amplified fragments. Fourteen mutations in the APC ge ne were characterized in 10/20 samples. Mutations in the KRAS and TP53 gene s were identified in 3/57 and 4/51 adenomas, respectively. The mutation fre quencies and distribution of mutations in APC correlate with published data on exophytic adenomas. The low mutation frequency of the TP53 gene is cons istent with the benign nature of the research material. KRAS activation (an early event in polypoid colorectal adenomas) apparently does not play a si gnificant role in nonpolypoid adenoma development bur may result in the dev elopment of a polypoid configuration. Genes Chromosomes Cancer 27:202-208, 2000. (C) 2000 Wiley-Liss, Inc.