Human epithelial ovarian cancer allelotype.
To determine which chromosomes and chromosomal regions contain putative tumor suppressor genes important for human epithelial ovarian cancer, we performed loss of heterozygosity (LOH) studies on 37 primary epithelial ovarian tumors. Using 70 polymorphic markers, we examined all chromosome arms (excluding acrocentric arms) on all specimens. Our findings show a high frequency of LOH for the following chromosome arms: 5q (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 statistically significant differences of LOH for the following chromosome arms: 6p (29% versus 70%); 13q (0% versus 72%); 17p (33% versus 90%); and 17q (29% versus 87%). No statistically significant difference was found between different histological subtypes. The average fractional allelic loss for low grade tumors was 0.17 versus 0.40 for high grade and 0.35 for all tumors. In an effort to more specifically localize common regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 13 (5 markers); chromosome 17 (8 markers); and chromosome 6 (8 polymorphic markers). No tumor showed deletion of only a portion of chromosome 13. When any informative marker for chromosome 13 showed loss, all markers showed loss. Similarly, the tumors of most patients demonstrated LOH of all informative markers that map to chromosome 17; however, regional deletion of 17p markers was observed in 3 tumors. Twelve tumors demonstrated regional deletions of portions of chromosome 6. These tumors suggest that at least 2 regions of chromosome 6 are important for ovarian epithelial carcinogenesis. One region appears to be on distal 6q and a second region is near the centromere of chromosome 6 proximal to the HLA locus.
Cliby
W
W
Department of Gynecologic Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Ritland
S
S
Hartmann
L
L
Dodson
M
M
Halling
K C
KC
Keeney
G
G
Podratz
K C
KC
Jenkins
R B
RB
D000483:Alleles; D001345:Autoradiography; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000502:physiology; D004848:Epithelium / Q000473:pathology / Q000502:physiology; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics