EBV-associated epigenetic signature in a colorectal cancer multicase family.

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Abstract Background: EBV is the first culprit virus that has been linked to human cancers. It has been shown recently to act through various epigenetic mechanisms, including DNA hypermethylation, EBV-related miRNA, and RNA editing enzymes. Methods: Whole exome sequencing of an extended multi-case colorectal cancer family revealed a potential oncogenic viral etiology. Investigation of such putative involvement in the same family was carried out by interrogating exome sequences of the tumor tissue for the presence of EBV signatures, in addition to immune histochemistry analysis and PCR of the LMP and EBER genes. Due to previously encountered strong signals for the involvement of APOBEC3b as an RNA editing enzyme, quantitative PCR was performed to quantify APOBEC3b. Various bioinformatics tools have also been used to detect virus-related miRNAs. Results: The EBV 2 sequence was retrieved from patient tumor sequences and detected by PCR and immunohistochemistry in the tumor samples. APOBEC3b was found to be sixfold higher in the sample than in controls, which explains the high C/T transition occurrence among tumor sequences. Bioinformatic analysis revealed that has-miR-29 b and has-miR-130 were among the top related miRNAs to EBV and colorectal cancer which was further supported by expression analysis. Conclusions: These results, in addition to expanding the list of EBV-related cancers, highlight potential epigenetic mechanisms that might help explain the oncogenic functionality of the virus and the ontology of tumor complexity.

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