Fragment analysis of the p53 gene in ovarian tumors

Abstract

he role of the p53 tumor suppressor gene inhuman carcinogenesis has been extensivelystudied. One central function of the p53 protein iscontrol of cellular growth after DNA damagethrough mechanisms involving growth arrest andapoptosis (1–3). These functions are believed to be atleast partially mediated by the ability of p53 to actas a transcription factor. Mutations in the p53 geneare found in most human malignancies and currentresearch is focusing on their role in cancer initiationand progression. p53 gene mutations can lead todefective cellular responses after DNA damage, dys-regulated cell growth, and tumor formation. Theidentification of p53 gene mutations in tumor cells isof diagnostic and therapeutic importance because:(a) tumors with a mutant p53 gene are usuallyresistant to certain chemotherapeutic agents or ra-diation; (b) a variety of tumors bearing a mutant p53gene have a less favorable prognosis than tumors ofthe same type with a wild-type p53 gene (4).The frequency of p53 gene mutations is high incancers of the colon (5), breast (6), lung (7), ovary (8),and brain (9). About 10% of the mutations aredeletions or insertions (10). Insertions range from 1to 14 nucleotides in length and in most cases, theinserted nucleotides duplicate the sequences of theneighboring region. Deletions range from 1 to 37nucleotides. Presence of deletions/insertions in 6 outof 11 newly established ovarian carcinoma cell lineshave been reported (11). In this report, we studiedthe presence of deletions and insertions in the p53gene in 89 primary ovarian tumors.