Presence of Viral DNA in Whole-Genome Sequencing of Brain Tumor Tissues from The Cancer Genome Atlas

Determining the potential role of viruses in brain tumorigen-esis has proven to be extremely elusive. Even with the devel-opment of newer technologies, establishing the presence of the virus, the temporality of the infection, and the influence of viral factors in carcinogenesis remains challenging. A few recent studies have contributed to the controversy surrounding the question of whether viral factors could explain a proportion of glioma risk (1–3). At least one such study has examined transcriptome se-quencing (RNA-Seq) data in an attempt to detect the presence of viral transcripts in brain tumor tissues and has failed to identify viral RNA transcripts or protein expression (1). Here, we wish to clarify how these data, alongwith our ownpreliminary findings on viral DNA sequences in tumor tissues, can contribute to our ever-evolving understanding of the associations between viruses and gliomagenesis. The absence of viral RNA transcripts, as detected by RNA-Seq, doesnotnecessarily indicate that thevirus isnotpresentor influential in the target tissue. It is possible that viruses that are expressed during transformation or in the early stages of carcinogenesis may enter latency or fail to be expressed due to cancer-associated mutations after the tumorhas developed. Theplausibility of this depends on the natural history of infection for each particular virus. Alternatively, some viruses may be able to contribute to the carcinogenic process without being expressed (4). Viruses that integrate their own DNA into the host’s genome can initiate insertionalmutagenesis.Hepatitis B virus and certain oncogenic avian viruses provide examples of vi-ruses that can spur carcinogenesis, at least partially, through this mechanism (5, 6). Therefore, studies that examine only RNA-Seq data may be unable to completely ascertain whether such viruses could be contributing to carcinogenesis. We recently examined whole-genome sequencing data, avail-able through The Cancer Genome Atlas (TCGA