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Increased Prevalence of K-ras Oncogene Mutations in Lung Adenocarcinoma¹

Department of Medicine, Divisions of Hematology [N. E. M., D. R. J.], Oncology [N. E. M.], Pulmonary and Critical Care Medicine [C. L. F., W. N. R.], and Environmental Medicine [N. D.] and Kaplan Comprehensive Cancer Center [D. R. J.], New York University Medical Center, New York, New York 10016

Reported estimates of ras mutation prevalence in lung adenocarcinoma of 15–24% may be underestimates because of the insensitivity of the assays used. We have devised a rapid, non-radioactive assay for ras mutations, which detects 1 mutant allele/10³ normal alleles and have used it to study DNA isolated from 53 lung tumor samples (including 28 adenocarcinomas) previously analyzed by PCR/allele specific oligonucleotide hybridization, which is less sensitive. We detected mutations in 13 of 28 samples, including 7 not detected by PCR/allele specific oligonucleotide hybridization. We also found ras mutations in 14 of 25 previously unstudied samples (56%). Our results indicate that the prevalence of K-ras codon 12 mutations in lung adenocarcinoma is higher than previously reported; thus, ras mutations may be more clinically useful as molecular markers for lung cancer than has been appreciated.

¹ This work was supported by National Cancer Institute Grant NIH (NCI) K12 CA01713-02 (N. E. M.), American Cancer Society Institutional Grant IRG-14-35 (D. R. J.) and National Institute of Environmental Health Sciences Grant NIH (NIEHS) T32 ES07267-02 (C. L. F., W. N. R.).

² To whom requests for reprints should be addressed, at Research Service 151, New York V.A. Hospital, 423 E. 23 St., New York, NY 10010.

Received 1/ 9/95. Accepted 2/20/95.

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