Characterization of fusion genes in common and rare epithelial ovarian cancer histologic subtypes

Madalene A. Earp, Rama Raghavan, Qian Li, Junqiang Dai, Stacey J. Winham, Julie M. Cunningham, Yanina Natanzon, Kimberly R. Kalli, Xiaonan Hou, S. John Weroha, Paul Haluska, Kate Lawrenson, Simon A. Gayther, Chen Wang, Ellen L. Goode, Brooke L. Fridley

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Gene fusions play a critical role in some cancers and can serve as important clinical targets. In epithelial ovarian cancer (EOC), the contribution of fusions, especially by histological type, is unclear. We therefore screened for recurrent fusions in a histologically diverse panel of 220 EOCs using RNA sequencing. The Pipeline for RNA-Sequencing Data Analysis (PRADA) was used to identify fusions and allow for comparison with The Cancer Genome Atlas (TCGA) tumors. Associations between fusions and clinical prognosis were evaluated using Cox proportional hazards regression models. Nine recurrent fusions, defined as occurring in two or more tumors, were observed. CRHR1-KANSL1 was the most frequently identified fusion, identified in 6 tumors (2.7% of all tumors). This fusion was not associated with survival; other recurrent fusions were too rare to warrant survival analyses. One recurrent in-frame fusion, UBAP1-TGM7, was unique to clear cell (CC) EOC tumors (in 10%, or 2 of 20 CC tumors). We found some evidence that CC tumors harbor more fusions on average than any other EOC histological type, including high-grade serous (HGS) tumors. CC tumors harbored a mean of 7.4 fusions (standard deviation [sd] = 7.4, N = 20), compared to HGS EOC tumors mean of 2.0 fusions (sd = 3.3, N = 141). Few fusion genes were detected in endometrioid tumors (mean = 0.24, sd = 0.74, N = 55) or mucinous tumors (mean = 0.25, sd = 0.5, N = 4) tumors. To conclude, we identify one fusion at 10% frequency in the CC EOC subtype, but find little evidence for common (> 5% frequency) recurrent fusion genes in EOC overall, or in HGS subtype-specific EOC tumors.

Original languageEnglish (US)
Pages (from-to)46891-46899
Number of pages9
JournalOncotarget
Volume8
Issue number29
DOIs
StatePublished - 2017

Keywords

  • Fusion gene
  • Histological subtypes
  • Ovarian cancer
  • RNA-sequencing
  • TCGA

ASJC Scopus subject areas

  • Oncology

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