Abstract 4889: Characterizing the viromes in pediatric cancers through whole genome sequencing

Abstract

Abstract Viral infections have been associated with the development of adult cancers such as cervical carcinomas and head/neck cancers. However, there is lack of clear understanding of the composition of virome in pediatric cancers. Here, we made the first attempt to identify differentially enriched viral communities in biological material from pediatric cancer patients, and to predict virus integration sites that may be associated with etiology or tumor progression of pediatric cancers. The Pediatric Cancer Genome project (PCGP) has previously generated whole-genome sequencing (WGS) data of matched cancer-normal samples for over 600 pediatric patients from three classes of cancers: leukemia, solid tumors, and central nervous system (CNS) cancers. We re-constructed the virome composition profiles in each sample based on the unmapped and partially mapped Illumina reads extracted from the PCGP WGS data. Taxonomic assignments of the extracted read data were conducted using the Kraken metagenomic pipeline and virus integration sites were predicted by the VyPER pipeline. Custom scripts were used for downstream comparative analyses. A comparison of the alpha diversity of each virome indicated that the tumor samples in general have a lower diversity compared to the normal samples across all tumor types. This trend holds true in leukemia, where both tumor and normal samples were blood derived, suggesting that this is not due to different origins of the tumor samples. Ordination analyses based on the viral composition identified distinct clusters in the three classes of cancers. These clusters were formed mainly by samples of medulloblastoma for CNS, T-ALL and hypodiploid B-ALL for leukemia, retinoblastoma and rhabdomyosarcoma for solid tumors. Viruses, such as phages, herpesviraidae and several sarcoma viruses, were differentially enriched in these clusters. Potential integration with retroviruses or herpesviruses was predicted at a high frequency. Less frequent integration events were also detected with known oncogenic viruses, such as simian virus 40 and human adenovirus C, which were under deep sequencing validation. In summary, our comprehensive characterization of the virome in a wide spectrum of pediatric cancers revealed a potential connection between specific viral communities and integration sites in certain distinct types of pediatric cancers. Our findings highlight a possible mechanism underlying the tumor progression in pediatric patients. Citation Format: Ti-Cheng Chang, John Easton, Emilia M. Pinto, Jinghui Zhang, Gang Wu. Characterizing the viromes in pediatric cancers through whole genome sequencing [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 4889. doi:10.1158/1538-7445.AM2017-4889