Recurrent Somatic Copy Number Alterations and Their Association with Oncogene Expression Levels in High-Grade Ovarian Serous Carcinoma
Author:
Esplen Hillary P.1ORCID, Yang Richard K.2ORCID, Kalia Awdhesh1, Tang Zhenya34ORCID, Tang Guilin3, Medeiros L. Jeffrey3ORCID, Toruner Gokce A.3ORCID
Affiliation:
1. Graduate Program in Diagnostic Genetics and Genomics, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA 2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA 3. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Avenue, Houston, TX 77030-4009, USA 4. Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-7815, USA
Abstract
Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly correlated for 274 genes; 24 genes were classified as a Tier 1 gene in the Cancer Gene Census in the Catalogue of Somatic Mutations in Cancer (CGC-COSMIC). Of these, 11 Tier 1 genes had highly correlated SCNA and mRNA expression levels: TBL1XR1, PIK3CA, UBR5, EIF3E, RAD21, EXT1, RECQL4, KRAS, PRKACA, BRD4, and TPM4. There was no association between gene amplification and disease stage or PFS. EIF3E, RAD21, and EXT1 were more frequently amplified in younger patients, specifically those under the age of 55 years. Patients with tumors carrying PRKACA, BRD4, or TPM4 amplification were associated with a significantly shorter OS. RECQL4 amplification was more frequent in younger patients, and tumors with this amplification were associated with a significantly better OS.
Funder
Michelle and Lee Yao Endowed Scholarship
Subject
Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics
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