K-ras mutation and loss of heterozygosity of chromosome 17p and survival in colorectal cancer.

Abstract

The development of colorectal cancer (CRC) is thought to be a multistage process involving alterations to several types of genes, including oncogenes and tumour suppressor genes. This study examined the associations between allelic deletions of chromosome 17p in the region of the p53 gene and K-ras gene mutation and survival among CRC patients. Resected specimens from 233 patients were examined. Point mutation of codon 12 of K-ras was assessed using a modified polymerase chain reaction method. Allelic deletion of 17p was demonstrated by loss of heterozygosity (LOH) with the marker Mfd144. Fifty-seven tumours (24%) showed somatic point mutation of codon 12 of K-ras and 86 tumours (37%) showed LOH of Mfd144. There were 107 tumours (46%) with either K-ras mutation or LOH and 18 tumours (8%) with both. Compared with patients with neither alteration, significantly poorer survival was experienced only by those with both alterations (P = 0.015). However, when this variable was introduced into a multivariate analysis controlling for the patient's age and tumour stage, it failed to show a statistically significant independent effect on survival. Point mutation of K-ras and LOH of Mfd144 in CRC does not add to the prognostic information already available from clinicopathological staging.