Characterization of p53 gene mutations in colorectal carcinomas from an Asian population

Abstract

A series of colorectal carcinomas from an Asian population in Singapore were analyzed for mutations in the tumor suppressor gene p53. Based on single-stand conformation polymorphism (PCR-SSCP) analysis and direct DNA sequencing, 15 of 38 tumors (39%) were found to contain mutations in exons 5-8 of the p53 gene. The point mutations were predominantly base transitions. Among the 10 transitions, 5 were at CpG dinucleotide sites. One-third (5/15) of the mutations were found at previously identified hotspot codons 175, 248 and 282. In one case an insertion of a 6-base pair sequence was found. p53 mutations did not correlate with tumor histological grade, Dukes' stage, or metastases. However, tumors at the distal site showed a higher proportion of mutations than the proximal site. Further, no mutation was found in the normal mucosa adjacent to tumor site, suggesting that no germ-line mutations were present. The results were compared with those from other studies and are discussed in connection to possible etiological factors that are specific to the local population.