P53 ALTERATIONS IN UTERINE LEIOMYOSARCOMAS VERSUS LEIOMYOMAS

Leiomyoma is the most common benign smooth muscle tumor. Although rare in other organs, it is frequent in the uterus, occurring in nearly 40% of women over 50 years of age. These benign tumors rarely undergo malignant transformation. The incidence of leiomyosarcomas in uterine leiomyomas is estimated to be between 0.13 and 0.29%. Little is known of the genetic abnormalities leading to this neoplasia. Loss of p53 function has been implicated in the pathogenesis of many human tumors. We evaluated eight leiomyosarcomas and eight leiomyomas for alterations in exons 5-8 of p53, which are the mutational hot-spots for this gene in human malignancies. Genomic DNA of the samples was studied by single-strand conformation polymorphism (SSCP) analysis and positive samples were analyzed by direct sequencing of PCR-amplified products. Each exon was studied individually, and positive controls were used for each exon. Three alterations in a total of eight leiomyosarcoma samples were found; the changes were point mutations (exon 5, codon 165; exon 8, codon 275; exon 8, codon 266). No alterations of p53 could be demonstrated in the eight leiomyoma samples. Our results show for the first time that p53 mutations are frequent in leiomyosarcomas, and one distinguishing difference between benign leiomyomas and some malignant leiomyosarcomas is the acquisition of a p53 mutation. (C) 1994 Academic Press, Inc.