Human endogenous retrovirus HERV-K(HML-2) activity in prostate cancer is dominated by a few loci

Goering, Wolfgang; Schmitt, Katja; Dostert, Melanie; Schaal, Heiner; Deenen, René; Mayer, Jens; Schulz, Wolfgang A.

doi:10.1002/pros.23095

Cited by 44 publications

(48 citation statements)

References 49 publications

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“…In comparison with healthy tissues, the higher expression of HERV-K in malignant diseases, like melanomas [27], ovarian cancer [28], breast cancer [29], prostate cancer [30], teratocarcinoma [31], have been investigated. Smoking or ultraviolet C could be the risk factors which may have an influence on the HERV-K expression [32, 33].…”

Section: Discussionmentioning

confidence: 99%

Human Endogenous Retroviruses-K (HML-2) Expression Is Correlated with Prognosis and Progress of Hepatocellular Carcinoma

Hong

Liu

et al. 2016

BioMed Research International

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Background. The association between human endogenous retroviruses-K (HERV-K) (HML-2) and human disease, including a variety of cancers, has been indicated. However, the function of HERV-K (HML-2) in the progression of hepatocellular carcinoma (HCC) still remains largely unclear. Methods. We detected the expression of HERV-K (HML-2) in 84 HCC tissues and adjacent nontumor tissues by quantitative real-time PCR (qRT-PCR) and analyzed its correlation with the clinical parameters. Result. The HEVR-K level was significantly increased in HCC compared with adjacent normal tissues (P < 0.01) which was proved to be significantly associated with cirrhosis (P < 0.05), tumor differentiation (P < 0.05), and TNM stage (P < 0.05). Moreover, the high expression of HERV-K (HML-2) had a poorer overall survival than patients with lower expression by a Kaplan-Meier survival analysis (P < 0.01). The multivariate Cox regression analysis indicated that the level of HERV-K (HML-2) was an independent prognostic factor for the overall survival rate of HCC patients. Receiver operating characteristic (ROC) curves demonstrated the diagnostic accuracy of HERV-K (HML-2) expression in HCC (AUC = 0.729, 74.7% sensitivity, and 67.8% specificity). Conclusions. Our results suggested that upregulation of HERV-K (HML-2) in HCC patients was significantly related to cancer progression and poor outcome, indicating that HERV-K (HML-2) might be a novel candidate prognostic biomarker for HCC.

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Section: Discussionmentioning

confidence: 99%

Human Endogenous Retroviruses-K (HML-2) Expression Is Correlated with Prognosis and Progress of Hepatocellular Carcinoma

Hong

Liu

et al. 2016

BioMed Research International

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“…Although not a common translocation, Tomlins et al identified a prostate tumor with the 5’ end of a HERV-K (HML-2) element on chromosome 22q11.23 fused to ETV1 [199]. This particular HERV-K element is a complex locus with two 5’ LTRs and is quite highly expressed in prostate cancer [200]. Indeed, while a possible function is unknown, this HERV-K locus produces a lncRNA annotated as PCAT-14, for prostate cancer–associated ncRNA transcript-14 [201].…”

Section: Introductionmentioning

confidence: 99%

Endogenous retroviral promoter exaptation in human cancer

2016

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Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs) with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs) provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

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“…Our results imply that there are more frequent alterations in the copy number of HERV coding sequences than previously appreciated, even for families that apparently have long ceased to be infectious or transpositionally active such as HERV-H and HERV-W (78,79). Overexpression of gene products encoded by these families as well as HERV-K has been documented in a number of conditions, including multiple sclerosis (MS) (18), amyotrophic lateral sclerosis (ALS) (22), rheumatoid arthritis (80), systemic lupus erythematosus (81), schizophrenia (82) and type 1 diabetes (83) and several cancers (84)(85)(86)(87). It remains uncertain whether overexpression of HERVs contributes to the etiology or progression of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Diverse endogenous retroviruses generate structural variation between human genomes via LTR recombination

Thomas

Perron

Feschotte

2018

Preprint

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Human endogenous retroviruses (HERVs) occupy a substantial fraction of the genome and impact cellular function with both beneficial and deleterious consequences. The vast majority of HERV sequences descend from ancient retroviral families no longer capable of infection or genomic propagation. In fact, most are no longer represented by full-length proviruses but by solitary long terminal repeats (solo LTRs) that arose via non-allelic recombination events between the two LTRs of a proviral insertion. Because LTR-LTR recombination events may occur long after proviral insertion but are challenging to detect in resequencing data, we hypothesize that this mechanism produces an underappreciated amount of genomic variation in the human population. To test this idea, we develop a computational pipeline specifically designed to capture such dimorphic HERV alleles from short-read genome sequencing data.When applied to 279 individuals sequenced as part of the Simons Genome Diversity Project, the pipeline retrieves most of the dimorphic variants previously reported for the HERV-K(HML2) subfamily as well as dozens of additional candidates, including members of the HERV-H and HERV-W families. We experimentally validate several of these candidates, including the first reported instance of an unfixed HERV-W provirus. These data indicate that human proviral content exhibit more extensive interindividual variation than previously recognized. These findings have important implications for our understanding of the contribution of HERVs to human physiology and disease.

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Human endogenous retrovirus HERV-K(HML-2) activity in prostate cancer is dominated by a few loci

Cited by 44 publications

References 49 publications

Human Endogenous Retroviruses-K (HML-2) Expression Is Correlated with Prognosis and Progress of Hepatocellular Carcinoma

Human Endogenous Retroviruses-K (HML-2) Expression Is Correlated with Prognosis and Progress of Hepatocellular Carcinoma

Endogenous retroviral promoter exaptation in human cancer

Diverse endogenous retroviruses generate structural variation between human genomes via LTR recombination

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