P53 POINT MUTATION AND SURVIVAL IN COLORECTAL-CANCER PATIENTS

We have examined the relationship between point mutation of the p53 tu mor suppressor gene and survival in colorectal cancer patients. We fou nd that patients with tumors harboring mutated p53 genes showed a sign ificantly poorer prognosis than did those patients with genes without point mutations, and, moreover, patient response to postoperative ther apies depended significantly on mutation status in both adjuvant and p alliative treatment cohorts. However, not all point mutations were the same functionally; point mutations within the conserved domains of th e p53 tumor suppressor gene were inherently more aggressive than tumor s with point mutations outside of these domains, and mutations of codo n 175 were particularly aggressive. These results suggest that knowled ge of a patient's p53 status, both with respect to the presence of poi nt mutations and to the specific nature of the lesion, may be required to accurately predict both the course of the disease and the response of the disease to postoperative therapeutic interventions, especially those therapies based on the induction of apoptosis in the neoplastic cell.