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Prostate Cancer
Volume 2019, Article ID 4047680, 11 pages
https://doi.org/10.1155/2019/4047680
Research Article

Interactions between Germline and Somatic Mutated Genes in Aggressive Prostate Cancer

Department of Genetics, Louisiana State University Health Sciences Center, School of Medicine, 533 Bolivar St., New Orleans, LA 70112, USA

Correspondence should be addressed to Chindo Hicks; ude.cshusl@3kcihc

Received 18 December 2018; Revised 29 January 2019; Accepted 15 February 2019; Published 17 March 2019

Academic Editor: Cristina Magi-Galluzzi

Copyright © 2019 Tarun Karthik Kumar Mamidi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Prostate cancer (PCa) is the most common diagnosed malignancy and the second leading cause of cancer-related deaths among men in the USA. Advances in high-throughput genotyping and next generation sequencing technologies have enabled discovery of germline genetic susceptibility variants and somatic mutations acquired during tumor formation. Emerging evidence indicates that germline variations may interact with somatic events in carcinogenesis. However, the possible oncogenic interactions and cooperation between germline and somatic variation and their role in aggressive PCa remain largely unexplored. Here we investigated the possible oncogenic interactions and cooperation between genes containing germline variation from genome-wide association studies (GWAS) and genes containing somatic mutations from tumor genomes of 305 men with aggressive tumors and 52 control samples from The Cancer Genome Atlas (TCGA). Network and pathway analysis were performed to identify molecular networks and biological pathways enriched for germline and somatic mutations. The analysis revealed 90 functionally related genes containing both germline and somatic mutations. Transcriptome analysis revealed a 61-gene signature containing both germline and somatic mutations. Network analysis revealed molecular networks of functionally related genes and biological pathways including P53, STAT3, NKX3-1, KLK3, and Androgen receptor signaling pathways enriched for germline and somatic mutations. The results show that integrative analysis is a powerful approach to uncovering the possible oncogenic interactions and cooperation between germline and somatic mutations and understanding the broader biological context in which they operate in aggressive PCa.