Mutational Activation of the K-ras Oncogene
S Rodenhuis, ML van de Wetering… - … England Journal of …, 1987 - Mass Medical Soc
S Rodenhuis, ML van de Wetering, WJ Mooi, SG Evers, N van Zandwijk, JL Bos
New England Journal of Medicine, 1987•Mass Medical SocTo define the role of cellular oncogenes in human cancers, we studied the prevalence of
mutational activation of ras oncogenes in untreated non-small-cell lung cancer. Genomic
DNA was extracted from 39 tumor specimens obtained by thoracotomy and was examined
for activating point mutations in codons 12, 13, and 61 of the H-ras, K-ras, and N-ras genes.
A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro
amplification step was employed. The K-ras gene was found to be activated by point …
mutational activation of ras oncogenes in untreated non-small-cell lung cancer. Genomic
DNA was extracted from 39 tumor specimens obtained by thoracotomy and was examined
for activating point mutations in codons 12, 13, and 61 of the H-ras, K-ras, and N-ras genes.
A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro
amplification step was employed. The K-ras gene was found to be activated by point …
Abstract
To define the role of cellular oncogenes in human cancers, we studied the prevalence of mutational activation of ras oncogenes in untreated non-small-cell lung cancer. Genomic DNA was extracted from 39 tumor specimens obtained by thoracotomy and was examined for activating point mutations in codons 12, 13, and 61 of the H-ras, K-ras, and N-ras genes. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed.
The K-ras gene was found to be activated by point mutations in codon 12 in 5 of 10 adenocarcinomas. Two of these tumors were less than 2 cm in size and had not metastasized. No ras gene mutations were observed in 15 squamous-cell carcinomas, 10 large-cell carcinomas, 1 carcinoid, 2 metastatic adenocarcinomas from primary tumors outside the lung, and 1 small-cell carcinoma. An approximately 20-fold amplification of the unmutated K-ras gene was observed in a tumor that proved to be a solitary lung metastasis of a rectal carcinoma.
We conclude that mutational K-ras activation may be an important early event in the pathogenesis of adenocarcinoma of the lung but that amplification of ras genes or mutational activation of H-ras or N-ras does not play a major part in non-small-cell lung cancer. (N Engl J Med 1987; 317:929–35.)
The New England Journal Of Medicine