Denaturing gradient cel electrophoresis screening of the BRCA1 gene in cells from precancerous cervical lesions

OBJECTIVE: To determine the integrity of the BRCA1 gene in archival, paraff in-embedded tissues from precancerous lesions of the uterine cervix. STUDY DESIGN: DNA was extracted from histologically documented precancerous cervical lesions (17 cases). Polymerase chain reactions were performed tar geting exon 11 of BRCA1 (434-bp), the L 1 consensus human papillomavirus (H PV) gene common to >25 HPV types, as well as the beta-globin gene. The ampl ified products were analyzed using denaturing gradient gel electrophoresis. RESULTS: Mutation of the BRCA1 exon 11 gene teas detected in >76% of cases with precancerous lesions of the cervix. The mutations were either complete deletions or deletions of one or move nucleotides, lending to frame shifts . There were Mo significant differences infrequency of BRCA1 mutations amon g precancerous cervical tissues positive for the HPV L1 consensus gene (n=9 ) when compared with HPV-negative tissues. CONCLUSION: The mutated BRCA1 gene was associated with 76% of 17 precancero us lesions of the cervix. The type of cervical intraepithelial neoplasia an d the presence or absence of HPV were not related to the mutations. The rol e of BRCA1 mutation in the genesis of precancerous cervical lesions needs t o be explored further.