Ras oncogene point mutation: an infrequent event in bronchioloalveolar cancer

Ras oncogene point mutation, primarily activating the K-ras gene, has been reported in approximately one third of lung adenocarcinomas. This identifies a subset of early stage tumors clinically associated with smoking and an aggressive clinical course. Because of these findings, this study was undertaken to determine the occurrence of ras point mutations in bronchioloalveolar carcinoma. This uncommon form of lung adenocarcinoma is usually indolent but can sometimes present as a rapidly growing, multifocal tumor. Twenty tumor samples obtained at thoracotomy were examined for H-ras, K-ras, and N-ras oncogene mutational activation involving codons 12, 13, or 61. This was performed by an oligonucleotide hybridization technique following polymerase chain reaction amplification of these specific sequences. K-ras point mutation involving codon 12 was observed in two tumors, but not in the adjacent histologically benign lung tissue. These mutations were confirmed by direct sequencing of these polymerase chain reaction products. Both patients were smokers, had stage I tumors, and remain disease-free at 27 and 40 months postoperatively. No H-ras or N-ras point mutations were found. These findings suggest that ras activation is an infrequent event in bronchioloalveolar carcinoma. We speculate that ras activation is not a common transformational event in this form of lung adenocarcinoma.