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Gender Differences in p53 Mutational Status in Small Cell Lung Cancer¹

Molecular Biology Laboratory at the Department of Thoracic/Head and Neck Medical Oncology [J. E. T., M. R., D. L., W. K. H., L. M.] and Department of Pathology [J. R.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Mutations in the p53 tumor suppressor gene have been demonstrated to be one of the most frequent genetic abnormalities in human cancers. Previous studies have shown that the frequency of p53 mutations is significantly higher in small cell lung cancer than in non-small cell lung cancer. However, this conclusion was based in large part on data derived from tumor cell lines and from studies with relatively small sample sizes and biased gender populations. To determine the mutational frequency in the p53 tumor suppressor gene and a potential difference in gender, we analyzed primary small cell lung cancer tumors from 65 patients (37 males and 28 females) for p53 mutations between exons 5 and 9. Mutations were found in 37 of 65 tumors (57%) within the region of p53 analyzed. Interestingly, none of the tumors from females contained more than one mutation, whereas four of the tumors from males contained more than one mutation. The most common mutation in this population was an adenosine-to-guanine transition (27%), followed by guanine-to-thymidine transversion (17%) and guanine-to-adenosine transition (12%). The gender difference in p53 mutational rate identified in this study suggests that a higher proportion of female tumors may develop through pathways not involving p53 mutations.