Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma

Cancer. 2012 Jun 1;118(11):2846-57. doi: 10.1002/cncr.26598. Epub 2011 Dec 2.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics*
  • Adenocarcinoma, Clear Cell / mortality
  • Adenocarcinoma, Clear Cell / therapy*
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 20
  • DNA Copy Number Variations
  • Disease-Free Survival
  • Female
  • Gene Amplification*
  • Gene Expression / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / therapy*
  • Prognosis
  • Trans-Activators / genetics*


  • Trans-Activators
  • ZNF217 protein, human