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Aberrations of the p53 Tumor Suppressor Gene in Human Non-Small Cell Carcinomas of the Lung¹

Oncogene Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome Chuo-ku Tokyo 104, Japan

Aberrations of the p53 gene in 115 surgical specimens of non-small cell carcinomas of the lung were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products. Structural abnormalities of the p53 gene were observed in 60 tumors (52%), i.e., 8 of 14 large cell carcinomas, 24 of 58 adenocarcinomas, 25 of 37 squamous cell carcinomas, and 3 of 6 adenosquamous carcinomas. Direct sequencing of abnormal DNA fragments revealed 45 single-base substitutions, 9 deletions or insertion of a short nucleotide sequence, and 3 two-base substitutions in 57 tumors. In the other 3 tumors, loss of one of the p53 alleles was observed, with no mutation in the other allele. Allelic loss of the p53 gene was observed in 14 of 43 informative cases (33%), and in 11 of the 14 cases the remaining allele was mutated. The aberrations of the p53 gene were not limited to a particular histological type or clinical stage. Their high frequency suggests that they were involved in the genesis of non-small cell carcinomas of the lung. The mutation frequency (46%) of the p53 gene in tumors carrying mutated ras genes was essentially the same as the overall frequency in lung cancers, suggesting that accumulation of mutations in these two genes in a tumor is a random phenomenon.

¹ This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control, Japan; a Grant-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture; a grant from the Special Coordination Fund of the Science and Technology Agency of Japan; a grant from the Princess Takamatsu Cancer Research Fund; and a grant from the Naito Foundation. Y. K. was the recipient of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research, Japan.

² To whom requests for reprints should be addressed.

Received 4/ 3/92. Accepted 6/18/92.

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