No significant viral transcription detected in whole breast cancer transcriptomes

Abstract

BackgroundStudies evaluating the presence of viral sequences in breast cancer (BC), including various strains of human papillomavirus and human herpes virus, have yielded conflicting results. Most were based on RT-PCR and in situ hybridization.MethodsIn this report we searched for expressed viral sequences in 58 BC transcriptomes using five distinct in silico methods. In addition, we complemented our RNA sequencing results with exome sequencing, PCR and immunohistochemistry (IHC) analyses. A control sample was used to test our in silico methods.ResultsAll of the computational methods correctly detected viral sequences in the control sample. We identified a small number of viral sequences belonging to human herpesvirus 4 and 6 and Merkel cell polyomavirus. The extremely low expression levels—two orders of magnitude lower than in a typical hepatitis B virus infection in hepatocellular carcinoma—did not suggest active infections. The presence of viral elements was confirmed in sample-matched exome sequences, but could not be confirmed by PCR or IHC.ConclusionsOur results show that no viral sequences are expressed in significant amounts in the BC investigated. The presence of non-transcribed viral DNA cannot be excluded.

The Distinctive Mutational Spectra of Polyomavirus-Negative Merkel Cell Carcinoma

“…Tumor-specific truncating LTAg mutations were not detected in mapped viral reads from these two tumors. Although this finding is of uncertain significance, the much lower number of viral reads in these two samples suggests background low level viral loads previously reported in non-MCC carcinoma, possibly representing background wild-type viral infection (19). Based on negative qPCR and immunohistochemistry, these tumors were categorized as MCPyV-negative.…”

Human Cancers and Mammalian Retroviruses: Should We Worry About Bovine Leukemia virus?

“…given BLVs role in bovine B cell leukaemia); and exome sequencing and RNAseq of breast cancer FFPE samples from Belgium also found no evidence of BLV or other retroviruses [11]. Conversely, a multi-pathogen probe-based array found evidence of retroviruses in a proportion of screened FFPE breast cancer samples [12], as well as other viral and bacterial pathogens.…”

“…As a result, since the mid-1990s studies have used primers complementary to regions of the MMTV genome with low homology to known HERVs, commonly targeted to the env region of MMTV which has just 16% homology to HERVK-10, the most closely related HERV. A recent systematic review of these refined molecular studies concluded that, while many studies detected MMTV env sequences in malignant tissue, various methodological flaws meant that none of the studies with a positive result were convincing[16].Fimereli et al harnessed multiple in silico techniques to analyse breast cancertranscriptomes for viral gene expression, and concluded that no viruses were expressed highly enough to be considered causative, furthermore MMTV-like sequences were not detected[11]. As discussed above, RNAseq and deep sequencing studies of breast cancer samples have produced mixed support for the presence of a retrovirus in human breast cancer.…”

No association between HPV positive breast cancer and expression of human papilloma viral transcripts

“…Using this approach it has been possible to identify a novel virus in organ transplant recipients 16 , HPV in squamous cell carcinoma of the head and neck 17 , hepatitis B virus in hepatocellular carcinoma 18 and Epstein Barr virus in gastric carcinoma 17 . However, to date, NGS approaches have failed to detect the expression of viral RNA (transcripts) in breast adenocarcinoma 17 19 20 . Moreover, only one study has examined whether a breast cancer sample that is positive for HPV DNA is also positive for HPV transcript 19 .…”

“…However, to date, NGS approaches have failed to detect the expression of viral RNA (transcripts) in breast adenocarcinoma 17 19 20 . Moreover, only one study has examined whether a breast cancer sample that is positive for HPV DNA is also positive for HPV transcript 19 . This study failed to find evidence of HPV transcript in the two HPV positive breast cancer samples examined.…”