Comparative genomic hybridization detects frequent overrepresentation of 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 carcinomas and two ovarian tumors of low malignant potential (LMP). Many of the carcinoma specimens displayed numerous imbalances. The most common sites of copy number increases, in order of frequency, were 8q24.1, 20q13.2-qter, 3q26.3-qter, 1q32, 20p, 9p21-pter, and 12p. DNA amplification was identified in 12 carcinomas (48%). The most frequent sites of amplification were 8q24.1-24.2, 3q26.3, and 20q13.2-qter. Other recurrent sites of amplification included 7q36, 17q25, and 19q13.1-13.2. The most frequent sites of copy number decreases were 5q21, 9q, 17p, 17q12-21, 4q26-31, 16q, and 22q. Underrepresentation of 17p was observed in six of 16 stage III/IV tumors, but in none of seven stage I/II tumors, suggesting that this change may be a late event associated with the transition of ovarian carcinomas to a more metastatic disease. Overrepresentation of 3q26.3-qter, 5p14-pter, 8q24.1, 9p21-pter, 20p, and 20q13.2-qter and underrepresentation of 4q26-31 and 17q12-21 also tended to be more common in advanced-stage tumors. All ten grade 3 tumors had copy number increases involving 8q24.1, compared to only three of nine 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 the two LMP tumors displayed chromosomal alterations, which consisted of overrepresentation of 5p and 9p only. Taken collectively, these findings and data from other CGH studies of ovarian cancers define a set of small chromosome segments that are consistently over- or underrepresented and, thus, highlight sites of putative oncogenes and tumor suppressor genes that contribute to the pathogenesis of these highly malignant neoplasms.
Sonoda
G
G
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Palazzo
J
J
du Manoir
S
S
Godwin
A K
AK
Feder
M
M
Yakushiji
M
M
Testa
J R
JR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations / Q000235:genetics*; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004273:DNA, Neoplasm / Q000302:isolation & purification; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm