Viral expression associated with gastrointestinal adenocarcinomas in TCGA high-throughput sequencing data

Abstract

BackgroundUp to 20% of cancers worldwide are thought to be associated with microbial pathogens, including bacteria and viruses. The widely used methods of viral infection detection are usually limited to a few a priori suspected viruses in one cancer type. To our knowledge, there have not been many broad screening approaches to address this problem more comprehensively.MethodsIn this study, we performed a comprehensive screening for viruses in nine common cancers using a multistep computational approach. Tumor transcriptome and genome sequencing data were available from The Cancer Genome Atlas (TCGA). Nine hundred fifty eight primary tumors in nine common cancers with poor prognosis were screened against a non-redundant database of virus sequences. DNA sequences from normal matched tissue specimens were used as controls to test whether each virus is associated with tumors.ResultsWe identified human papilloma virus type 18 (HPV-18) and four human herpes viruses (HHV) types 4, 5, 6B, and 8, also known as EBV, CMV, roseola virus, and KSHV, in colon, rectal, and stomach adenocarcinomas. In total, 59% of screened gastrointestinal adenocarcinomas (GIA) were positive for at least one virus: 26% for EBV, 21% for CMV, 7% for HHV-6B, and 20% for HPV-18. Over 20% of tumors were co-infected with multiple viruses. Two viruses (EBV and CMV) were statistically significantly associated with colorectal cancers when compared to the matched healthy tissues from the same individuals (p = 0.02 and 0.03, respectively). HPV-18 was not detected in DNA, and thus, no association testing was possible. Nevertheless, HPV-18 expression patterns suggest viral integration in the host genome, consistent with the potentially oncogenic nature of HPV-18 in colorectal adenocarcinomas. The estimated counts of viral copies were below one per cell for all identified viruses and approached the detection limit.ConclusionsOur comprehensive screening for viruses in multiple cancer types using next-generation sequencing data clearly demonstrates the presence of viral sequences in GIA. EBV, CMV, and HPV-18 are potentially causal for GIA, although their oncogenic role is yet to be established.

HeLa Nucleic Acid Contamination in The Cancer Genome Atlas Leads to the Misidentification of Human Papillomavirus 18

“…However, our analyses show that these alignments match the portion of the HPV18 genome that is integrated into the HeLa genome and do not represent a different strain of HPV18. In contrast to previous reports, our data suggest that HPV18 is not present in the non-CESC samples, such as the colon adenocarcinoma, rectum adenocarcinoma (READ), and normal kidney samples, as previously reported (19,20). These findings are most likely explained by contamination with HeLa nucleic acids during sample procurement, preparation, or sequencing.…”

“…Therefore, it is not surprising that we only detected HPV18 by WXS in CESC samples. A recent study reported that HPV18 was not present in whole-genome sequencing (WGS) of the same COAD and READ samples for which HPV18 was detected in the corresponding RNA-Seq analyses (20). These results make sense in light of the fact that none of the TCGA WXS and WGS samples were sequenced in the centers (UNC-LCCC and BCCAGSC) where HeLa contamination was found.…”

“…High-risk HPV has also been detected in colorectal samples, but these findings remain controversial (16)(17)(18). Recently, HPV18 has been detected in colorectal samples and a normal kidney sample in The Cancer Genome Atlas (TCGA) database (19,20). In these reports, the pattern of viral transcription is indicative of oncogenic integration.…”

Original paper Epstein-Barr virus DNA in colorectal carcinoma in Iranian patients

“…Contrary to the many positive reports [27][28][29], certain papers have suggested a lack of a direct relationship between this virus and the development of CRC.…”

Identification of human cytomegalovirus in tumour tissues of colorectal cancer and its association with the outcome of non-elderly patients

“…Some earlier studies reported negative detection of HCMV in the tumour tissue of CRC (Akintola-Ogunremi et al, 2005;Boguszakova et al, 1988;Brichacek et al, 1980). However, more and more recent data have indicated that HCMV preferentially infects the tumour tissue of CRC (Cai et al, 2016;Dimberg et al, 2013;Li et al, 2015;Salyakina & Tsinoremas, 2013;Sole et al, 2015;Tafvizi & Fard, 2014;Taher et al, 2014). There is also a growing body of evidence suggesting that HCMV plays an oncomodulatory role and affects the disease course of human cancers.…”