High frequency of allelic imbalance at regions of chromosome arm 8p in ovarian carcinoma.
Progressive genetic changes such as the inactivation of tumor suppressor genes (TSG) are thought to play an important role in the initiation and progression of ovarian cancer. Frequent nonrandom allelic imbalance (AI) at 8p11-p21 and 8p22-pter suggests the existence of TSGs that may be involved in the carcinogenesis of several human malignancies. We investigated 70 ovarian tumors with 11 highly polymorphic markers spanning 8p12-p21 and 8p22-pter to produce an AI map of 8p in epithelial ovarian cancer. Allelic imbalance was demonstrated in 54 tumors (77%), most frequently occurring at D8S136 (54%) and at D8S1992 (55%). Poorly differentiated and advanced stage cancers were more often affected by AI (G1+G2 vs. G3; 20% vs. 66%; stage I+II vs. III+IV, 36% vs. 54%, P<.001; Kruskal-Wallis test) than well differentiated and early stage tumors. There was no relationship between histological subtype and AI. Smallest regions of overlap (SRO) were delineated by analyzing 38 tumors with partial AI. This study provides compelling evidence for the involvement of TSGs on the short arm of chromosome 8, at 8p12-p21 and at 8p23 in the development and progression of epithelial ovarian cancer.
Pribill
I
I
Department of Medicine I, Clinical Division of Oncology, University Hospital, Molecular Oncology Group, Währingergürtel 18-20, A-1090 Vienna, Austria.
Speiser
P
P
Leary
J
J
Leodolter
S
S
Hacker
N F
NF
Friedlander
M L
ML
Birnbaum
D
D
Zeillinger
R
R
Krainer
M
M
D022981:Allelic Imbalance; D002898:Chromosomes, Human, Pair 8; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology