Alterations of p14~(ARF) and p53 genes in human primary colorectal carcinomas / 中国病理生理杂志

ABSTRACT

AIM: To investigate the genetic and epigenetic alterations of p14~ ARF gene and mutation status of p53 gene in human primary colorectal carcinomas and to analyze the relationship between the two gene changes and the role of abrogation of the p14~ ARF -p53 pathway in colorectal carcinogenesis. METHODS: The homozygous deletions, mutations, methylation of 5′ CpG islands, mRNA expression of p14~ ARF gene and mutations of p53 gene were assessed by PCR, direct sequencing, methylation-specific PCR, and RT-PCR in the tumorous and matched adjacent normal colorectal tissues from 56 patients with colorectal carcinoma. RESULTS: ① p14~ ARF alterations were detected in 27% (15/56) of colorectal carcinoma tissues studied, of which 1 case showed homozygous deletion, 14 cases showed 5′ CpG island methylation, and no mutation was found in any tumor. ②15 colorectal carcinomas with p14~ ARF alterations indicated lack of (13 cases) or at low level of expression (2 cases) of p14~ ARF mRNA, while expression of the p14~ ARF transcript was detected in the remaining 41 colorectal carcinomas and any matched adjacent normal colorectal tissues. ③ The mutations of p53 gene were detected in 48% (27/56) of colorectal carcinomas investigated. ④ Of these 56 cases, 12 had p14~ ARF alterations alone, 24 had p53 mutations alone, 3 had both p53 mutations and p14~ ARF methylation, and 17 had neither. 70% (39/56) of the samples had either or both abnormalities of the two genes, and p14~ ARF hypermethylation was related to wildtype p53 (P