title: Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers.
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.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Katahira
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Isamu
authors.initials: I
authors.lastname: Ishiwata
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
authors.forename: Masaomi
authors.initials: M
authors.lastname: Takayama
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C414585:TGIF2 protein, human; D015534:Trans-Activators; C113698:ZNF217 protein, human