ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma

PLoS Biol. 2011 Sep;9(9):e1001156. doi: 10.1371/journal.pbio.1001156. Epub 2011 Sep 20.

Abstract

Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5' exons of ESRRA, encoding a ligand-independent member of the nuclear-hormone receptor superfamily, to the 3' exons of C11orf20, a conserved but uncharacterized gene located immediately upstream of ESRRA in the reference genome. To estimate the prevalence of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and sequencing and confirmed its presence in 10 of these. Targeted resequencing of the corresponding genomic region from two fusion-positive tumor samples identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream of C11orf20 in one tumor, and evidence of local copy number variation in the ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion transcript may play a role in pathogenesis of a substantial fraction of serous ovarian cancers and could provide a molecular marker for detection of the cancer. Gene fusions involving adjacent or nearby genes can readily escape detection but may play important roles in the development and progression of cancer.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Biomarkers, Tumor / genetics*
  • Canada
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 11 / chemistry
  • Chromosomes, Human, Pair 11 / genetics*
  • Cystadenocarcinoma, Serous / epidemiology
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / pathology
  • DNA Copy Number Variations
  • Exons
  • Female
  • Humans
  • Molecular Sequence Data
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / epidemiology
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Oncogene Proteins, Fusion / genetics*
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Prevalence
  • RNA, Messenger
  • Receptors, Estrogen / genetics*
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA
  • United States

Substances

  • Biomarkers, Tumor
  • ERRalpha estrogen-related receptor
  • ESRRA-C11orf20 fusion protein, human
  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • Receptors, Estrogen