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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Buekers
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Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, 4630 JCP, 200 Hawkins Drive, Iowa City, Iowa 52242, USA.
Lallas
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Buller
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D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D010051:Ovarian Neoplasms / Q000235:genetics*; D014960:X Chromosome
D004273:DNA, Neoplasm