Upregulation of human endogenous retrovirus-K (HML-2) mRNAs in hepatoblastoma: Identification of potential new immunotherapeutic targets and biomarkers.

Journal of Pediatric Surgery
David F GrabskiSara K Rasmussen

Abstract

Hepatoblastoma is the most common liver malignancy in children. In order to advance therapy against hepatoblastoma, novel immunologic targets and biomarkers are needed. Our purpose in this investigation is to examine hepatoblastoma transcriptomes for the expression of a class of genomic elements known as Human Endogenous Retrovirus (HERVs). HERVs are abundant in the human genome and are biologically active elements that have been associated with multiple malignancies and proposed as immunologic targets in a subset of tumors. A sub-family of HERVs, HERV-K(HML-2) (HERV-K), have been shown to be tightly regulated in fetal development, making investigation of these elements in pediatric tumors paramount. We first created a HERVK-FASTA file utilizing 91 previously described HML-2 proviruses. We then concatenated the file onto the GRCh38.95 cDNA library from Ensembl. We used this reference database to evaluate existing RNA-seq data from 10 hepatoblastoma tumors and 3 normal liver controls (GEO accession ID: GSE8977575). Quantification and differential proviral expression analysis between hepatoblastoma and normal liver controls was performed using the pseudo-alignment program Salmon and DESeq2, respectively. HERV-K mRNA was expressed...Continue Reading

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Citations

May 1, 2021·Cancers·Annacarmen PetrizzoLuigi Buonaguro

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