Comparative analysis of p16/CDKN2, p53 and ras gene alterations in human non-small cell lung cancers, with and without associated pulmonary asbestosis.

Abstract

To investigate genetic abnormalities in human non-small cell lung carcinomas (NSCLC) associated with pulmonary asbestosis as compared with nou-asbestos linked lung cancers, twenty-nine primary non-small cell lung carcinomas (NSCLC) were examined for genetic abnormalities of p16/CDKN2, p53 and ras genes by single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP) and direct sequencing. Ten specimens were obtained from autopsies in which concurrent pulmonary asbestosis was present, while 19 samples were surgical specimens from asbestosis-free patients. K-ras mutations were detected in 10% each of the cancers from both asbestosis and non-asbestosis cases. p16/CDKN2 deletions or mutations and p53 aberrations were demonstrated in 20% and 10% of tumors from asbestosis cases, whereas, 32% and 21% of the cancers, respectively, from asbestosis-free patients were positive. In conclusion, it is suggested that the enhancement of neoplasia in the lung by asbestos is not dependent on suppression of p16/CDKN2 and p53 or ras activation and therefore, that asbestosis may activate alternate tumorigenic pathways in the development of NSCLC.