Abstract 5550: Collaborative analyses for delineating mutation variations among different ethnic patients of prostate cancer based on genomic data integration

Abstract

Abstract Emerging data support the hypothesis that both inherited and somatic alterations of genomes of African American (AA) prostate cancer (CaP) patients are significantly different from that of Caucasian American (CA) men. Recent studies from our and other groups have established that frequencies of the most common genomic alteration, TMPRSS2-ERG fusion, which apparently causes the high expression of ERG oncoprotein, is markedly lower in AA than in CA patients. Some works indicated that the frequency of CaP ERG fusion is the lowest in Asian patients, but this frequency changed from 11% to 78% in different Asian cohorts. Further analysis in Asian men is necessary. In order to systematically and comprehensively address this and related problems, Uniformed Services University of the Health Sciences-Center for Prostate Disease Research (CPDR), the US National Cancer Institute (NCI) and CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), China, launched an international collaboration project. The overall goal of the project is to evaluate difference of driver gene mutations of prostate cancer in various ethnic groups by integrating genomic and transcriptomic data from CPDR, TCGA and the Chinese Prostate Cancer Consortium (CPCC), specially focusing on somatic alterations (ERG and others), microbiome, mitochondrial sequences and microRNAs. We integrated gene fusion, copy number, and gene expression data to detect potential driver genes and, as anticipated ERG alteration was one of the most commonly detected. The frequency of ERG fusion is the highest for CA, intermediate for AA and the lowest for Asian men, while its expression is significantly higher in ERG-fusion tumors than other tumors cross over all of the three ethnic groups. We did find some genes altered more frequently in Asian patients than in American patients, subject to further validations. We explored the methodology for microbiota profiling using prostate cancer WGS sequencing data. To this date, we have developed an analysis pipeline for the detection of microbiome from prostate tumor tissues and the corresponding blood samples with high confidence but inadequate sensitivity likely due to the low availability of both microbial sequences and bacterial reference genomes. Our preliminary analyses highlight the potential of international collaboration. CPDR-PICB-NCI will work on a seamless approach for data integration, particularly of the raw data to truly enhance CaP diagnosis and treatment by providing more informative biomarker and therapy targets relevant to ethnically diverse patient populations. Citation Format: Qingyu Xiao, Yidi Sun, Hong Li, Yixue Li, Guo-Ping Zhao, Wendy Wang, Sudhir Srivastava. Collaborative analyses for delineating mutation variations among different ethnic patients of prostate cancer based on genomic data integration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5550. doi:10.1158/1538-7445.AM2017-5550