K-rasOncogene Activation as a Prognostic Marker in Adenocarcinoma of the Lung

作者：Robert J.C. Slebos, Robert E. Kibbelaar, Otilia Dalesio, A. Kooistra, Jacob Stam, Chris J.L.M. Meijer, Sjoerd Sc. Wagenaar, R.G.J.R.A. Vanderschueren, Nico van Zandwijk, Wolter J. Mooi, Johannes L. Bos, Sjoerd Rodenhuis · 发表于：New England Journal of Medicine · 年份：1990 · DOI：10.1056/nejm199008303230902 · 被引用次数：810 · 研究领域：Lung Cancer Treatments and Mutations、Protein Kinase Regulation and GTPase Signaling、PI3K/AKT/mTOR signaling in cancer

BACKGROUND: The capability of activated oncogenes to induce malignant transformation of immortalized cells in vitro has suggested that they have a similar role in the pathogenesis of human tumors. We previously found that activation of the K-ras oncogene by a point mutation in codon 12 occurs in about one third of human lung adenocarcinomas. METHODS: We studied the clinical importance of this oncogene-activation in 69 patients with lung adenocarcinoma in whom complete resection of the tumor was possible. The polymerase chain reaction was used to amplify ras-specific sequences of DNA isolated from frozen or paraffin-embedded tumor samples. Ras point mutations were subsequently detected and classified with the use of mutation-specific oligonucleotide probes. RESULTS: Nineteen of the tumors harbored a point mutation in codon 12 of the K-ras oncogene. There was no association between the K-ras point mutation and the age at diagnosis, sex, or presence of previous or concurrent neoplasms. Tumors positive for K-ras point mutations tended to be smaller and less differentiated than those without mutations. The K-ras codon-12 point mutation was a strong (and unfavorable) prognostic factor: 12 of the 19 patients with K-ras point-mutation-positive tumors died during the follow-up period, as compared with 16 of the 50 patients with no mutation in the K-ras oncogene (P = 0.002). This difference in prognosis was also reflected in the duration of disease-free survival (P = 0.038) and in the ...