Xp22.2-3 loss of heterozygosity is associated with germline BRCA1 mutationin ovarian cancer

Objective. X-Chromosome loss of heterozygosity (LOH) occurs in approximatel y 40% of ovarian cancers. We have previously demonstrated an association be tween nonrandom X-chromosome inactivation and germline BRCA1 mutation, The current study examines the association between X-chromosome LOH and BRCA1 m utation. Methods. Ninety tumor DNA (81 ovary, 5 fallopian tube, 4 primary peritoneal ) and matched peripheral blood mononuclear cell DNA samples were examined f or LOH with 11 X-chromosome microsatellite DNA markers. Results.Tumor DNA demonstrated frequent LOH at the Xp22.2-3 region (37.7% a t DXS6807), Loss of heterozygosity on Xp was twice as common in tumor DNA f rom germline BRCA1 mutation carriers (9/14 vs 19/67, P = 0.02), In four eva luable samples, Xp22.2-3 LOH preferentially occurred from the active X alle le. Conclusions. Our data support the hypothesis that an Xp22.2-3 gene product interacts with or modifies the expression of BRCA1 in some hereditary ovari an cancers. (C) 2000 Academic Press.