Genetic Aberrations Detected by Comparative Genomic Hybridization in Ovarian Clear Cell Adenocarcinomas

Abstract

Genetic abnormalities were detected by comparative genomic hybridization (CGH) in 12 ovarian clear cell adenocarcinomas. DNA sequence copy number abnormalities (CNAs) occurring in more than 20% of the cancers included increased copy numbers of 8q11-q13, 8q21-q22, 8q23, 8q24-qter, 17q25-qter, 20q13-qter and 21q22-qter and reduced copy numbers of 19p. Increases in copy numbers of 8q11-q13, 8q21-q22, 8q23 and 8q24-qter occurred more frequently in disease-free patients than in recurrent/non-surviving patients (p < 0.05). However, increases in copy numbers of 17q25-qter and 20q13-qter occurred more frequently in recurrent/non-surviving patients than in disease-free patients (p < 0.05). Furthermore, increases in copy numbers of 17q25-qter and 20q13-qter occurred together (p < 0.05). Additionally, there were negative correlations between increases in copy numbers of 8q21-q22 and 17q25-qter, and between 8q21-q22 and 20q13-qter (p < 0.05). It appears that ovarian clear cell adenocarcinomas can be classified into two subtypes, one being cancer with an increase in copy numbers of 8q and the other being cancer with increases in copy numbers of 17q25-qter and 20q13-qter.

Expression Microarrays

“…Because chromosomes 3 and 8 have been previously shown to be subject to rearrangement and copy number change (12)(13)(14) and were found to be commonly involved in rearrangements by SKY and/or CGH, we performed a more detailed expression evaluation of cDNA mapping to these chromosomes. We identified a contiguous distribution of reduced expression of seven genes mapping to 3p25.5-3p21.3 interval and increased expression of four genes from 3q13.33-3q28 that were consistent with loss of 3p and gain of 3q in this and other CGH studies of ovarian cancer (17)(18)(19)(20)(21)(22)(23)(24)(25). Within the 3q13.33-3q28 interval, it is noteworthy that there was elevated expression of the calcium-sensing receptor (55) that has been previously shown to induce human ovarian surface epithelial cells to modulate extracellular calcium and induce proliferation.…”

“…Previous CGH studies (17)(18)(19)(20)(21)(22)(23)(24) have identified a similar pattern of genomic change, and attempts have been made to correlate these data with clinical endpoints (53). Studies by Yonescu et al (54) and Jenkins et al (11) show that structural and numerical changes predominantly occur on chromosome 11 endometrioid tumors.…”

“…To date, CGH has been widely used (17)(18)(19)(20)(21)(22)(23)(24)(25) in studying ovarian carcinomas and has identified increased copy numbers at 1q32, 3q26, 8q24.1-q24.2, 20q13.2-qter and frequent chromosomal losses identified at 5q21, 9q, 17p, 17q12-q21, 4q26-q31, 16q, and 22q. Sites of amplification have been identified at 7q36, 8q24.1-q24.2, 3q26.3, 17q25, 19q13.1-q13.2, and 20q13.2-qter by CGH.…”

PPM1D Is a Potential Therapeutic Target in Ovarian Clear Cell Carcinomas

“…Nonetheless, frequent gains of 8q (9,10), 17q (9,11), which has been associated with poorer prognosis in ovarian clear cell carcinoma, and 20q (9), and loss of 9p (12) have been reported. Importantly, very few high-resolution CGH studies have been done in ovarian clear cell carcinoma (13) and no candidate therapeutic targets have hitherto been clearly identified and validated in these studies.…”

Cytogenetic alterations in ovarian clear cell carcinoma detected by comparative genomic hybridisation

“…The cytogenetics of 12 cases of clear cell ovarian carcinoma assessed by CGH has been reported by Suehiro et al (2000). This Japanese study, which included eight cases of FIGO stage I disease, demonstrated amplification of chromosome 8q in eight cases (67%).…”