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

X-Chromosome loss of heterozygosity (LOH) occurs in approximately 40% of ovarian cancers. We have previously demonstrated an association between nonrandom X-chromosome inactivation and germline BRCA1 mutation. The current study examines the association between X-chromosome LOH and BRCA1 mutation.,Ninety tumor DNA (81 ovary, 5 fallopian tube, 4 primary peritoneal) and matched peripheral blood mononuclear cell DNA samples were examined for LOH with 11 X-chromosome microsatellite DNA markers.,Tumor DNA demonstrated frequent LOH at the Xp22.2-3 region (37.7% at DXS6807). Loss of heterozygosity on Xp was twice as common in tumor DNA from germline BRCA1 mutation carriers (9/14 vs 19/67, P = 0.02). In four evaluable samples, Xp22.2-3 LOH preferentially occurred from the active X allele.,Our data support the hypothesis that an Xp22.2-3 gene product interacts with or modifies the expression of BRCA1 in some hereditary ovarian cancers.