The p53 gene is very frequently mutated in small-cell lung cancer with a distinct nucleotide substitution pattern

Abstract

The p53 gene has been implicated as a tumor-suppressor gene whose disruption is involved in the pathogenesis of common human cancers. The results of extensive analysis of p53 mutations in non-small cell lung cancers (NSCLCs) have revealed that p53 is mutated in 45% of NSCLC with base changes different from those of colon cancer. In this study, we examined 17 SCLC tumor samples taken directly from 15 patients as well as the corresponding nine tumor cell lines. Mutations changing the p53 coding sequence were found in 11 of 15 patients (73.3%) and showed a similar but distinct nucleotide substitution pattern compared with NSCLC, suggesting that a different mutagenic process is involved. In addition, a strong correlation was seen between the presence of p53 mutations in tumors and the successful establishment of the corresponding cell lines, suggesting that p53 mutations can confer a selective growth advantage in vitro (and probably also in vivo).