Somatic copy number alterations associated with Japanese or endometriosis in ovarian clear cell adenocarcinoma

PLoS One. 2015 Feb 6;10(2):e0116977. doi: 10.1371/journal.pone.0116977. eCollection 2015.

Abstract

When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC) include 1) a higher incidence among Japanese, 2) an association with endometriosis, 3) poor prognosis in advanced stages, and 4) a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH) to identify somatic copy number alterations (SCNAs) associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC. The entire 8q chromosome (minimum corrected p-value: q = 0.0001) and chromosome 20q13.2 including the ZNF217 locus (q = 0.0078) were amplified significantly more in Japanese than in Korean or German samples. This copy number amplification of the ZNF217 gene was confirmed by quantitative real-time polymerase chain reaction (Q-PCR). ZNF217 RNA levels were also higher in Japanese tumor samples than in non-Japanese samples (P = 0.027). Moreover, endometriosis was associated with amplification of EGFR gene (q = 0.047), which was again confirmed by Q-PCR and correlated with EGFR RNA expression. However, no SCNAs were significantly associated with prognosis or thrombosis. These results indicated that there may be an association between CCC and ZNF217 amplification among Japanese patients as well as between endometriosis and EGFR gene amplifications.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics*
  • Adenocarcinoma, Clear Cell / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group / genetics
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 20*
  • Chromosomes, Human, Pair 8*
  • Comparative Genomic Hybridization
  • Endometriosis / genetics*
  • ErbB Receptors / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / therapy
  • Real-Time Polymerase Chain Reaction
  • Trans-Activators / genetics

Substances

  • Trans-Activators
  • ZNF217 protein, human
  • EGFR protein, human
  • ErbB Receptors

Associated data

  • GEO/GSE47443

Grant support

The Ministry of Education, Culture, Sports, Science and Technology in the Japan-Supported Program for the Strategic Research Foundation at Private Universities and by the Jikei University School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Chugai Pharmaceutical Co., Ltd. provided support in the form of salaries for authors YA and NI, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.