Integrating germline and somatic variation information using genomic data for the discovery of biomarkers in prostate cancer

• Published in: BMC cancer Vol. 19; no. 1; p. 229
• Main Authors: Mamidi, Tarun Karthik Kumar, Wu, Jiande, Hicks, Chindo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.03.2019; BioMed Central; BMC
• Subjects: Analysis; Androgen receptors; Biochemistry; Biological markers; Biomarkers; Biomarkers, Tumor - genetics; Cancer genetics; Cancer research; Care and treatment; Consortia; Data processing; Disease susceptibility; Gene Expression; Gene Expression Regulation, Neoplastic; Gene mutation; Gene Regulatory Networks; Genes; Genetic analysis; Genetic aspects; Genetic Predisposition to Disease; Genetic susceptibility; Genome-Wide Association Study; Genomes; Genomic analysis; Genomics; Genomics - methods; Genotyping; Germ-Line Mutation; Germline somatic mutations genomic analysis prostate Cancer; Humans; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Male; Malignancy; Mutation; Myc protein; Ontology; p53 Protein; Patient outcomes; Platelet-derived growth factor; Prostate cancer; Prostatic Neoplasms - genetics; Proto-Oncogene Proteins c-myc - genetics; PTEN Phosphohydrolase - genetics; PTEN protein; Receptors, Androgen - genetics; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumorigenesis; Tumors; United States; United States > US; Germline somatic mutations genomic analysis prostate Cancer
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5440-8

Prostate cancer (PCa) is the most common diagnosed malignancy and the second leading cause of cancer-related deaths among men in the United States. High-throughput genotyping has enabled discovery of germline genetic susceptibility variants (herein referred to as germline mutations) associated with an increased risk of developing PCa. However, germline mutation information has not been leveraged and integrated with information on acquired somatic mutations to link genetic susceptibility to tumorigenesis. The objective of this exploratory study was to address this knowledge gap. Germline mutations and associated gene information were derived from genome-wide association studies (GWAS) reports. Somatic mutation and gene expression data were derived from 495 tumors and 52 normal control samples obtained from The Cancer Genome Atlas (TCGA). We integrated germline and somatic mutation information using gene expression data. We performed enrichment analysis to discover molecular networks and biological pathways enriched for germline and somatic mutations. We discovered a signature of 124 genes containing both germline and somatic mutations. Enrichment analysis revealed molecular networks and biological pathways enriched for germline and somatic mutations, including, the PDGF, P53, MYC, IGF-1, PTEN and Androgen receptor signaling pathways. Integrative genomic analysis links genetic susceptibility to tumorigenesis in PCa and establishes putative functional bridges between the germline and somatic variation, and the biological pathways they control.