p53 mutations in malignant gliomas

Abstract

A population-based series of incident cases of malignant glioma were analyzed for mutations in the tumor suppressor gene p53. Exons 4-8 were screened using PCR-single-strand conformation analysis and confirmed through direct sequencing. Of 62 tumors analyzed, 12 (19%) contained mutations in p53: one 18-bp duplication in exon 5, five point mutations in exon 4, three point mutations in exon 7, two point mutations in exon 8, and a splice-site mutation at the exon 6/intron 7 boundary. In contrast to previous studies of malignant glioma, the prevalence of transversion mutations (56%) was higher than transition mutations (33%). A large proportion of transversion mutations occurred in exon 4, a region that is not routinely screened in gliomas. We present here an improved method for screening exon 4 (and other GC-rich regions) of p53 using PCR-single-strand conformation analysis. The high frequency of transversion mutations suggests a role for exogenous carcinogens in the etiology of malignant glioma.