We have developed a virus detection and discovery computational pipeline, Pickaxe, and applied it to NGS databases provided by The Cancer Genome Atlas (TCGA). We analyzed a collection of whole genome (WGS), exome (WXS), and RNA (RNA-Seq) sequencing libraries from 3052 participants across 22 different cancers. NGS data from nearly all tumor and normal tissues examined contained contaminating viral sequences. Intensive computational and manual efforts are required to remove these artifacts. We found that several different types of cancers harbored Herpesviruses including EBV, CMV, HHV1, HHV2, HHV6 and HHV7. In addition to the reported associations of Hepatitis B and C virus (HBV & HCV) with liver cancer, and Human papillomaviruses (HPV) with cervical cancer and a subset of head and neck cancers, we found additional cases of HPV integrated in a small number of bladder cancers. Gene expression and mutational profiles suggest that HPV drives tumorigenesis in these cases.

我们已经开发了病毒检测和发现计算管道Pickaxe，并将其应用到The Cancer Genome Atlas（TCGA）提供的NGS数据库中。我们分析了来自22种不同癌症的3052名参与者的全基因组（WGS），外显子组（WXS）和RNA（RNA-Seq）测序文库的集合。来自几乎所有检查过的肿瘤和正常组织的NGS数据均包含污染的病毒序列。需要大量的计算和手动工作才能消除这些伪像。我们发现几种不同类型的癌症都带有疱疹病毒，包括EBV，CMV，HHV1，HHV2，HHV6和HHV7。除了已报道的乙型和丙型肝炎病毒（HBV和HCV）与肝癌，人乳头瘤病毒（HPV）与宫颈癌以及部分头颈癌的相关性，我们发现了其他合并在少数膀胱癌中的HPV病例。基因表达和突变谱表明，在这些情况下，HPV驱动肿瘤发生。