High frequency of allelic imbalance at regions of chromosome arm 8p in ovarian carcinoma

Progressive genetic changes such. as the inactivation of tumor suppressor g enes (TSG) are thought to play an important role in the initiation and prog ression of ovarian cancer. Frequent nonrandom allelic imbalance (AI) at 8p1 1 similar to p21 and 8p22 similar to pter suggests the existence of TSGs th at may be involved in the carcinogenesis of several human malignancies. We investigated 70 ovarian tumors with 11 highly polymorphic markers spanning 8p12 similar to p21 and 8p22 similar to 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%). Poor ly 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. Th is study provides compelling evidence for the involvement of TSGs on the sh ort arm of chromosome 8, at 8p12 similar to p21 and at 8p23 in the developm ent and progression of epithelial ovarian cancer. (C) 2001 Elsevier Science Inc. Ali rights reserved.