Loss of heterozygosity at chromosome 9q22-31 is a frequent and early event in ovarian tumors.
Loss of heterozygosity (LOH) studies in ovarian tumors, have highlighted the chromosomal regions at 9q22-31 and 9q32-34 as being potentially important in tumor development. We have investigated LOH at 9q22-31 in 85 patients with epithelial ovarian cancer, 15 with non-epithelial tumors and 16 with benign disease. Varying patterns of LOH were observed across the markers used between different tumors, the most common (71%) being interstitial discontinuous losses. LOH was frequent, and was detected at equally high levels in malignant (71%) and benign tumors (70%). LOH occurred in epithelial invasive tumors, borderline tumors, fibromas and dermoid tumors. In malignant epithelial tumors LOH at 9q22-31 was not significantly associated with patient clinical and pathological parameters; however, survival was 29 months at the 50th centile survival, in those women whose tumors displayed LOH compared with 60 months in women whose tumors retained heterozygosity. LOH at 9q22-31 was significantly associated with LOH at the p53 locus (p=0.02) and the ovarian suppressor locus at 3p21 (p=0.05). We conclude that the chromosome region at 9q22-31, flanked by the microsatellite markers D9S1796 and D9S53, is a frequent and early event in ovarian tumorigenesis. With the of extent of discontinuous LOH, high density deletion mapping of this region using LOH as a strategy to identify candidate genes may be problematic. However with the completion of the human genome sequencing project several candidate genes are identified.
Byrom
Jennifer
J
Institute for Science and Technology in Medicine, Keele University School of Medicine, University Hospital of North Staffordshire, Stoke-on-Trent, UK.
Mudaliar
Vivek
V
Redman
Charles W
CW
Jones
Peter
P
Strange
Richard C
RC
Hoban
Paul R
PR
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003131:Combined Modality Therapy; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D018283:Cystadenocarcinoma, Papillary / Q000235:genetics / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D003884:Dermoid Cyst / Q000235:genetics / Q000473:pathology; D005260:Female; D005350:Fibroma / Q000235:genetics / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate