HUMAN EPITHELIAL OVARIAN-CANCER ALLELOTYPE

To determine which chromosomes and chromosomal regions contain putativ e tumor suppressor genes important for human epithelial ovarian cancer , we performed loss of heterozygosity (LOH) studies on 37 primary epit helial ovarian tumors. Using 70 polymorphic markers, we examined all c hromosome arms (excluding acrocentric arms) on all specimens. Our find ings show a high frequency of LOH for the following chromosome arms: 5 q (43%); 6p (62%); 6q (57%); 7p (36%); 8p (40%); 9q (54%); 13q (56%); 14q (47%); 15q (36%); 17p (81%); 17q (76%); 18q (43%); 21q (36%); and 22q (71%). When separated into low and high grade tumors, there were s tatistically significant differences of LOH for the following chromoso me arms: 6p (29% versus 70%); 13q (0% versus 72%); 17p (33% versus 90% ); and 17q (29% versus 87%). No statistically significant difference w as found between different histological subtypes. The average fraction al allelic loss for low grade tumors was 0.17 versus 0.40 for high gra de and 0.35 for all tumors. In an effort to more specifically localize common regions of molecular genetic deletion, we examined the followi ng chromosomes in greater detail: chromosome 13 (5 markers); chromosom e 17 (8 markers); and chromosome 6 (8 polymorphic markers). No tumor s howed deletion of only a portion of chromosome 13. When any informativ e marker for chromosome 13 showed loss, all markers showed loss. Simil arly, the tumors of most patients demonstrated LOH of all informative markers that map to chromosome 17; however, regional deletion of 17p m arkers was observed i n 3 tumors. Twelve tumors demonstrated regional deletions of portions of chromosome 6. These tumors suggest that at le ast 2 regions of chromosome 6 are important for ovarian epithelial car cinogenesis. One region appears to be on distal 6q and a second region is near the centromere of chromosome 6 proximal to the HLA locus.