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Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers
Takafumi Watanabe1, Issei Imoto, Tomoyuki Katahira
1Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Abstract:
Frequent amplification of DNA at 20q or part of 20q has been demonstrated by comparative genomic hybridization in ovarian cancer (OC), but the genetic target(s) of these amplification events remain unknown. We examined copy-number changes with respect to six candidate genes, E2F1 (20q11.2), TGIF2 (20q11.2), AIB1 (20q12), PTPN1 (20q13.1), ZNF217 (20q13.2), and BTAK (20q13), and then measured transcription levels of each candidate in 18 OC cell lines. Three distinct cores of amplification were identified: 20q11.2, harboring E2F1 and TGIF2 (region I; 1 of 18 cell lines, 5.6%); 20q13.1, harboring PTPN1 (region II; 5 lines, 27.8%); and 20q13.2, harboring ZNF217 and BTAK (region III; 6 lines, 33.3%). Among the six genes examined, expression levels of PTPN1 and ZNF217 were significantly correlated with absolute copy-number, and those of PTPN1 and TGIF2 were significantly correlated with copy-number relative to the centromere of chromosome 20 (20cen). Among 19 primary OCs examined, moreover, we observed amplification of TGIF2, PTPN1 and ZNF217 in five (26.3%), ten (52.6%), and twelve (63.2%) tumors, respectively. Expression levels of PTPN1 and ZNF217 were significantly correlated with their copy-numbers in those primary OCs. Our results suggest that 20q amplifications in OCs can be extensive and complex, probably due to synergistic or non-synergistic amplification of separate regions of 20q, involving multiple, independently amplified targets.
Insights
Frequent DNA amplifications at 20q in ovarian cancer (OC) involve multiple genes. This study identified distinct amplification regions and correlated gene expression with copy-number changes, suggesting complex genetic targets in OC development.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Comparative genomic hybridization reveals frequent DNA amplifications on chromosome 20q in ovarian cancer (OC).
- The specific genetic targets driving these 20q amplifications in OC remain largely unidentified.
Purpose of the Study:
- To investigate copy-number alterations and transcription levels of six candidate genes (E2F1, TGIF2, AIB1, PTPN1, ZNF217, BTAK) located on chromosome 20q in OC.
- To identify distinct amplification cores and their correlation with gene expression in OC cell lines and primary tumors.
Main Methods:
- Analysis of copy-number changes and gene expression using comparative genomic hybridization and quantitative PCR in 18 OC cell lines.
- Examination of amplification patterns and gene expression in 19 primary OC tumors.
Main Results:
- Three distinct amplification cores were identified on 20q, involving genes E2F1, TGIF2, PTPN1, ZNF217, and BTAK.
- Expression levels of PTPN1 and ZNF217 significantly correlated with copy-number in both OC cell lines and primary tumors.
- Amplification of TGIF2, PTPN1, and ZNF217 was observed in a substantial proportion of primary OC samples.
Conclusions:
- 20q amplifications in ovarian cancer are complex and can involve multiple, independently amplified genetic targets across distinct chromosomal regions.
- PTPN1 and ZNF217 are likely key targets of 20q amplification in ovarian cancer, influencing tumor development.