Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung

• Published in: Cancer research (Chicago, Ill.) Vol. 48; no. 20; pp. 5738 - 5741
• Main Authors: RODENHUIS, S, SLEBOS, R. J. C, BOOT, A. J. M, EVERS, S. G, MOOI, W. J, WAGENAAR, S. S, VAN BODEGOM, P. C, BOS, J. L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-10-1988
• Subjects: Adenocarcinoma - genetics; Biological and medical sciences; Codon; Gene Expression Regulation; Genes, ras; Humans; Lung Neoplasms - genetics; Medical sciences; Mutation; Oncogenes; Pneumology; Smoking; Tumors of the respiratory system and mediastinum; Adenocarcinoma; Human; Respiratory disease; C-Onc gene; Cytogenetics; Tumor; Activation; Bronchopulmonary
• ISSN: 0008-5472; 1538-7445

47 tumor samples, 45 of which were obtained at thoracotomy for non-small cell lung cancer were examined for mutational activation of the oncogenes H-ras, K-ras, and N-ras. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. ras gene mutations were present in nine of 35 adenocarcinomas of the lung (all K-ras), in two of two lung metastases of colorectal adenocarcinomas (1 x K-ras, 1 x N-ras) and in one adenocarcinoma sample obtained at autopsy (H-ras). All K-ras and H-ras mutations were in either position 1 or 2 of codon 12, while the N-ras mutation was in position 2 of codon 61. The potential clinical significance of K-ras activation was analyzed using the combined results of this and of our earlier study (S. Rodenhuis et al., New Engl. J. Med., 317: 929-935, 1987). Lung adenocarcinomas with K-ras mutations tended to be smaller and were less likely to have spread to regional lymph nodes at presentation. With a median follow up of 10 months, survival data are still immature. None of six adenocarcinomas of nonsmokers had a K-ras mutation and only one of four who had stopped smoking more than 5 years before. We conclude that mutational K-ras activation is present in about a third of adenocarcinomas of the lung and that the mutational event may be a direct result of one or more carcinogenic ingredients of tobacco smoke. Studies involving larger numbers of patients are required to confirm the association of K-ras activation with smoking and the inverse relation with tumor progression.