title: Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma.
abstract: BACKGROUND
  The goal of this study was to examine the clinical significance of ZNF217 amplification and assess whether ZNF217 could be a potential therapeutic target in ovarian clear cell carcinoma (OCCC).
  
  
  METHODS
  ZNF217 expression and amplification in OCCC was assessed by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected via a retrospective chart review. ZNF217 gene knockdown using silencing RNA (siRNA) was used to assess ZNF217 functions in OCCC cell lines.
  
  
  RESULTS
  Gene amplification was identified in 12 of 60 (20.0%) OCCCs. ZNF217 copy number correlated significantly with ZNF217 protein expression (r = 0.341; P<.01). ZNF217 amplification correlated significantly with shorter progression-free (P = .0042) and overall (P = .0199) survival. There were nonsignificant trends between high ZNF217 protein expression and poor progression-free (P = .2594) and overall (P = .2199) survival. Multivariate analysis revealed ZNF217 gene amplification to be an independent prognostic factor for progression-free and overall survival after standard platinum agent-based chemotherapy (P = .0339 and P = .031, respectively). Profound growth inhibition and apoptosis were observed in ZNF217 siRNA-treated cancer cells with gene amplification compared with cancer cells with ZNF217 moderate expression without ZNF217 gene amplification or with low ZNF217 expression.
  
  
  CONCLUSIONS
  These findings indicate that ZNF217 overexpression is critical to growth and survival of OCCCs with ZNF217 gene amplification. Furthermore, they suggest that ZNF217 siRNA-induced phenotypes depend on amplification status of OCCCs. Therefore, ZNF217-targeted therapy may benefit OCCC patients with ZNF217 amplification.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Mohammed Tanjimur
authors.initials: MT
authors.lastname: Rahman
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Munmun
authors.initials: M
authors.lastname: Rahman
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakayama
authors.forename: Masako
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Atsuko
authors.initials: A
authors.lastname: Katagiri
authors.forename: Kouji
authors.initials: K
authors.lastname: Iida
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakayama
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Otsuki
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D045744:Cell Line, Tumor; D002890:Chromosomes, Human, Pair 20; D056915:DNA Copy Number Variations; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D015534:Trans-Activators; C113698:ZNF217 protein, human