Amplification of the NSD3‑BRD4‑CHD8 pathway in pelvic high‑grade serous carcinomas of tubo‑ovarian and endometrial origin

  • Authors:
    • Derek H. Jones
    • Douglas I. Lin
  • View Affiliations

  • Published online on: June 8, 2017     https://doi.org/10.3892/mco.2017.1289
  • Pages: 301-307
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Abstract

Identification of novel therapeutics in pelvic high‑grade serous carcinoma (HGSC) has been hampered by a paucity of actionable point mutations in target genes. The aim of the present study was to investigate the extent of amplification of the therapeutically targetable NSD3‑CHD8‑BRD4 pathway in pelvic HGSC, and to determine whether amplification is associated with worse prognosis. The Cancer Genome Atlas (TCGA) ovarian and endometrial cancer cohorts were retrospectively analyzed via online data‑mining tools to test the association of NSD3, CHD8 and BRD4 genomic alterations with survival of pelvic HGSC patients. It was demonstrated that amplification of the NSD3‑CHD8‑BRD4 pathway in the ovarian HGSC cohort (observed in 18% of the cases, 88/489) was significantly associated with worse overall and progression‑free survival compared with non‑amplified cases. In addition, amplification of NSD3, CHD8 and BRD4 also occurred in 9% (21/232) of overall endometrial cancer TCGA cases, which was associated with worse overall survival. In the endometrial cancer TCGA cohort, NSD3, CHD8 and BRD4 amplification occurred specifically in the serous carcinoma (25%, 13/53) and ‘serous‑like’ copy number high endometrial carcinoma (33%, 20/60) subgroups, compared with the polymerase e (0%, 0/17), microsatellite instability high (0%, 0/65) or low copy number (1%, 1/90) subgroups. These findings support the hypothesis that amplification of the NSD3‑BRD4‑CDH8 axis is frequent in pelvic HGSC of both ovarian and endometrial origin, and that this pathway is potentially targetable in a subset of HGSC patients.

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August-2017
Volume 7 Issue 2

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Spandidos Publications style
Jones DH and Lin DI: Amplification of the NSD3‑BRD4‑CHD8 pathway in pelvic high‑grade serous carcinomas of tubo‑ovarian and endometrial origin. Mol Clin Oncol 7: 301-307, 2017.
APA
Jones, D.H., & Lin, D.I. (2017). Amplification of the NSD3‑BRD4‑CHD8 pathway in pelvic high‑grade serous carcinomas of tubo‑ovarian and endometrial origin. Molecular and Clinical Oncology, 7, 301-307. https://doi.org/10.3892/mco.2017.1289
MLA
Jones, D. H., Lin, D. I."Amplification of the NSD3‑BRD4‑CHD8 pathway in pelvic high‑grade serous carcinomas of tubo‑ovarian and endometrial origin". Molecular and Clinical Oncology 7.2 (2017): 301-307.
Chicago
Jones, D. H., Lin, D. I."Amplification of the NSD3‑BRD4‑CHD8 pathway in pelvic high‑grade serous carcinomas of tubo‑ovarian and endometrial origin". Molecular and Clinical Oncology 7, no. 2 (2017): 301-307. https://doi.org/10.3892/mco.2017.1289