Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up to 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the only lineage still proliferating in the genome after the human-chimpanzee split, have intact open reading frames, some encoding for accessory genes called np9 and rec that interact with oncogenic pathways. Many studies have established that the transient expression of ERVs are in both stem cells and cancers results in aberrant self-renewal and uncontrolled proliferation.The wealth of high-quality genomic and transcriptomic Illumina sequence data available from The Cancer Genome Atlas (TCGA) that are sequenced from a diversity of different tumour types makes it a valuable resource in cancer research. However, there is currently no universal computational method for inferring expression of specific repetitive elements from RNA-seq data, such as genes encoded by HERV-K (HML-2).This study presents a novel and a highly specific pipeline that is able to capture and measure transcription of np9 and rec encoded by proviruses that share great sequence similarity, and are transcribed at very low levels. We show by using our novel methodology that np9 and rec are overexpressed in breast cancer, germ cell tumours, skin melanoma, lymphoma, ovarian cancer, and prostate cancer compared to non-diseased tissues. We also show that np9 and rec are specifically expressed in the 8 and 16-cell stage in human preimplantation embryos.

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the youngest lineage in the human genome, have intact open reading frames, some encoding for accessory genes called np9 and rec that interact with oncogenic pathways. Many studies have established that ERVs are transiently expressed in both stem cells and cancer, resulting in aberrant self-renewal and uncontrolled proliferation. np9 and rec expression are significantly correlated with a range of cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) biomarkers, including cellular receptors, transcription factors, and histone modifiers. Surprisingly, these ERV genes are negatively correlated with genes known to promote pluripotency in embryonic stem cell lines, such as Oct4. These results indicate that HERV-K (HML-2) is part of the transcriptional landscape responsible for cancer cells undergoing the phenotypic switch that characterises EMT. The discovery of np9 and rec 's correlation with CSC and EMT biomarkers suggest a yet undescribed role affecting the transitional CSC-like state in EMT and the shift towards cancer malignancy.