MUTANT K-RAS ONCOGENES IN COLON CANCERS DO NOT PREDICT PATIENTS CHEMOTHERAPY RESPONSE OR SURVIVAL

One half of human colon cancers bear mutant c-K-ras oncogenes. Mutant K-ras oncogenes are associated with shortened survival in non-small ce ll lung cancers, and, in cell line models, with resistance to cis-plat inum and to ionizing radiation. This study examines whether mutant K-r as alleles in colon cancer alter patients' response to chemotherapy or survival. We studied 37 patients who received chemotherapy with 5-flu orouracil and leucovorin. Exon 1 of the c-K-ras gene was PCR amplified from DNA extracted from paraffin-embedded tumor blocks. The presence of mutant or wild-type c-K-ras alleles was determined by dideoxy seque ncing of the PCR-amplified c-K-ras DNA. c-K-ras mutations at codons 12 or 13 were present in 19 and absent in 18 cases. Responses to chemoth erapy were equally likely in patients with either wild-type or mutant c-K-ras, occurring in 28% of patients with wild-type ras and 32% of pa tients with mutant ras (P = 0.8). Survival was also indistinguishable among both groups. Median survival from diagnosis was 35 months for ra s wild-type patients and 31 months for ras mutant patients (P = 0.96). Median survival from starting chemotherapy was 14 months for ras wild -type patients and 17 months for ras mutant patients (P = 0.26). Patie nts with colon cancers bearing either wild-type or mutant c-K-ras alle les are indistinguishable in overall survival and are equally likely t o respond to 5-fluorouracil-based chemotherapy.