Markowitz S, Hines JD, Lutterbaugh J, Myeroff L, Mackay W, Gordon N, Rustum Y, Luna E, Kleinerman J
Department of Medicine, University Hospitals of Cleveland, Cleveland, Ohio.
Clin Cancer Res. 1995 Apr;1(4):441-5.
One half of human colon cancers bear mutant c-K-ras oncogenes. Mutant K-ras oncogenes are associated with shortened survival in non-small cell lung cancers, and, in cell line models, with resistance to cis-platinum and to ionizing radiation. This study examines whether mutant K-ras alleles in colon cancer alter patients' response to chemotherapy or survival. We studied 37 patients who received chemotherapy with 5-fluorouracil 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 sequencing 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 chemotherapy 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 patients with mutant ras (P = 0.8). Survival was also indistinguishable among both groups. Median survival from diagnosis was 35 months for ras 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). Patients with colon cancers bearing either wild-type or mutant c-K-ras alleles are indistinguishable in overall survival and are equally likely to respond to 5-fluorouracil-based chemotherapy.
人类结肠癌中有一半携带突变型c-K-ras癌基因。突变型K-ras癌基因与非小细胞肺癌患者生存期缩短有关，并且在细胞系模型中与对顺铂和电离辐射的耐药性有关。本研究旨在探讨结肠癌中的突变型K-ras等位基因是否会改变患者对化疗的反应或生存期。我们研究了37例接受5-氟尿嘧啶和亚叶酸化疗的患者，从石蜡包埋肿瘤块提取的DNA中通过PCR扩增c-K-ras基因的外显子1。通过对PCR扩增的c-K-ras DNA进行双脱氧测序来确定突变型或野生型c-K-ras等位基因的存在。19例患者存在密码子12或13处的c-K-ras突变，18例患者不存在。野生型或突变型c-K-ras患者对化疗的反应可能性相同，野生型ras患者中有28%出现反应，突变型ras患者中有32%出现反应（P = 0.8）。两组患者的生存期也无差异。ras野生型患者从诊断开始的中位生存期为35个月，ras突变型患者为31个月（P = 0.96）。ras野生型患者从开始化疗起的中位生存期为14个月，ras突变型患者为17个月（P = 0.26）。携带野生型或突变型c-K-ras等位基因的结肠癌患者在总生存期方面无差异，对基于5-氟尿嘧啶的化疗反应的可能性也相同。
