Allelic loss on chromosome arm 8p: Analysis of sporadic epithelial ovariantumors

Objective. Our objective was to determine the frequency of allelic loss at 8p21 in sporadic epithelial ovarian cancer. We recently described allelic l oss at this locus in 7/9 ovarian cancers from patients with BRCA1 gene muta tions. Methods, We anonymously obtained and examined 40 unselected invasive epithe lial ovarian cancers and 5 low-malignant-potential (LMP) ovarian tumors for loss of heterozygosity (LOH) at 8p12-22, Pure epithelial and stromal cell populations were procured selectively by laser capture microdissection and extracted DNA was amplified with polymorphic microsatellite markers spannin g the region of interest. Results. LOH was highest (50%) at marker D8S136 located at 8p21 with 15 of 30 informative cases exhibiting an allelic deletion. None of the LMP tumors evaluated showed LOH at 8p12-22. A trend toward more frequent LOH at 8p12- 22 was identified with increasing disease aggressiveness from LMP to early stage invasive ovarian cancer to advanced stage invasive ovarian cancer (Le hman's test, P-2 < 0.024). Conclusions. Fifty percent allelic loss at the distal portion of 8p21 has n ot been reported to date for sporadic epithelial ovarian carcinomas, The hi gher rate of loss in our cohort, in contrast to previous allelotyping studi es, is due likely to analysis from homogenous cell populations. These resul ts, in concert with our previous study of BRCA1 mutation-positive patients, suggest a tumor suppressor gene locus at 8p21 for epithelial ovarian cance r.