Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer.

摘要: The INK4a-ARF locus encodes two tumor suppressor proteins involved in cell-cycle regulation, p16INK4a and p14ARF, whose functions are inactivated many human cancers. aim of this study was to evaluate p14ARF gene inactivation its association with some clinocopathological parameters colon cancer. mutational methylation status the genes analyzed 60 primary carcinomas 8 cancer cell lines. We have identified first reported mutations affecting exon 1beta HCT116 line one carcinomas. Both occur within N-terminal region documented as important for nucleolar localization interaction Mdm2. Tumor-specific found 33% 32% carcinomas, respectively. Methylation inversely correlated p53 overexpression (p = 0.02). significantly more frequent right-sided than left-sided tumors occurred frequently well-differentiated adenocarcinomas 0.005), whereas often methylated poorly differentiated 0.002). present results underline role development carcinoma. They suggest that profile specific genes, particular p16INK4a, might be related biologically distinct subsets possibly different tumorigenic pathways.