Conserved region mutations of the p53 gene are concentrated in distal colorectal cancers.

Abstract

Distal colorectal cancers, especially those in the rectum, are more aggressive and more commonly recurrent than proximal cancers. We studied the possible relationship between p53-gene mutation type and location of the tumour, since mutations in the conserved areas of the p53 gene have been suggested to result in a poorer outcome of colorectal cancer than mutations outside these areas. Exons 5 to 8 of the p53 gene were studied in specimens from 72 colorectal-cancer patients. Polymerase-chain-reaction-amplified products of tumour DNA were analyzed by automated direct sequencing. Of the mutations detected in distal cancers, 71% were located in conserved regions of the gene, while only 42% of the mutations in proximal cancers were in these areas. In rectal cancers, 81% of the mutations were located in conserved regions. The tumours with mutations in the conserved regions were more often poorly differentiated (23%) than those with other mutations (0%). Our results indicate that mutations in the conserved regions of the p53 gene accumulate in distal but not in proximal tumours. This difference may be related to the more aggressive behaviour and to different aetiological factors associated with distal tumours.