COMPARATIVE GENOMIC HYBRIDIZATION DETECTS FREQUENT OVERREPRESENTATIONOF CHROMOSOMAL MATERIAL FROM 3Q26, 8Q24, AND 20Q13 IN HUMAN OVARIAN CARCINOMAS

We used comparative genomic hybridization (CGH) to identify recurrent chromosomal imbalances in tumor DNA from 25 malignant ovarian carcinom as and two ovarian tumors of low malignant potential (LMP). Many of th e carcinoma specimens displayed numerous imbalances. The most common s ites of copy number increases, in order of frequency, were 8q24.1, 20q 13.2-qter, 3q26.3-qter, 1q32, 20p, 9p21-pter, and 12p. DNA amplificati on was identified in 12 carcinomas (48%). The most frequent sites of a mplification were 8q24.1-24.2, 3q26.3, and 20q13.2-qter. Other recurre nt; sites of amplification included 7q36, 17q25, and 19q13.1-13.2. The most frequent sites of copy number decreases were 5q21, 9q, 17p, 17q1 2-21, 4q26-31, 16q, and 22q. Underrepresentation of 17p was observed i n six of 16 stage III/IV tumors, but in none of seven stage I/II tumor s, suggesting that this change may be a late event associated with the transition of ovarian carcinomas to a more metastatic disease. Overre presentation of 3q26.3-qter, 5p14-pter, 8q24.1, 9p21-pter, 20p, and 20 q13.2-qter and underrepresentation of 4q26-31 and 17q12-21 also tended to be more common in advanced-stage tumors. All ten grade 3 rumors ha d copy number increases involving 8q24.1, compared to only three of ni ne grade 2 tumors. Overrepresentation of 3q26.3-qter and 20q13.2-qter was also observed at a higher frequency in high-grade tumors. One of t he two LMP tumors displayed chromosomal alterations, which consisted o f overrepresentation of 5p and 9p only. Taken collectively, these find ings and data from other CGH studies of ovarian cancers define a set o f small chromosome segments that are consistently over- or underrepres ented and, thus, highlight sites of putative oncogenes and tumor suppr essor genes chat contribute to the pathogenesis of these highly malign ant neoplasms. (C) 1997 Wiley-Liss, Inc.