High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach

Abstract

Background Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data. Methods In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads. Results Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found. Conclusions Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.

Contamination Issue in Viral Metagenomics: Problems, Solutions, and Clinical Perspectives

“…That was the case in the study linking febrile Kenyan adults with Kadiprio virus, which was initially considered to be the causative agent but was eventually found to be a part of QIAamp Viral RNA Mini Kit (Qiagen) kitome ( Ngoi et al, 2016 ). In a recent study, Mollerup et al (2019) used NGS to search for viruses in human cancers and found Merkel cell polyomavirus (MCPyV) in Merkel cell carcinomas. However, close similarity of all MCPyV sequences found across samples allowed studies to conclude laboratory surfaces as the source of contamination ( Foulongne et al, 2011 ; Mollerup et al, 2019 ).…”

Enteric Virome and Carcinogenesis in the Gut

“…Microscopic techniques like transmission electron microscopy (TEM) have not only benefited our understanding of viral structure, but they have also aided in the support of novel virus identification from shotgunbased sequencing studies [39,40,94,95]. Perhaps the most comprehensive study characterizing viruses from a variety of sample types associated with the development of various cancers utilized a diverse selection enrichment method targeting all major viral groups followed by high-throughput sequencing [96]. This study investigated total DNA and RNA, mRNA, retroviral [97] and vertebrate viral capture [98], as well as enrichment of small circular DNA capture [99].…”

Microbiome and cancer

“…Recent studies have indicated that global virome signatures may serve as markers of cancer development. Viral metagenomic signatures have been detected in lung adenocarcinoma biopsies (Cai et al, 2021) and more than 100 tumor samples, including oral, breast, colon, and genitourinary cancers (Mollerup et al, 2019). Cantalupo et al suggested that HPV, a known cause of cervical cancer and potentially other genitourinary cancers, is additionally correlated with tumor progression in head and neck cancers as well as bladder cancers (Cantalupo et al, 2018;IARC, 2009).…”