Abstract Genomic transposable elements (TEs) constitute a substantial portion of the non-protein-coding genome and play crucial roles in gene expression, regulation, evolution, and genomic variation. The human genome comprises both protein-coding and non-protein-coding regions, the latter often referred to as the “dark genome.” Key components of this non-coding region include non-coding RNAs (ncRNAs), transposable elements (TEs) or “jumping genes,” protein-coding genes of unknown function (e.g., SLX4IP, HSF2BP, and ELFN), and repetitive sequences such as Long Interspersed Nuclear Elements (LINEs), Short Interspersed Nuclear Elements (SINEs), and Human Endogenous Retroviruses (HERVs). While approximately 23,000 genes are known to encode proteins, nearly 98% of the genome is non-coding, previously dismissed as “junk DNA.” This non-coding compartment is composed of LINEs (∼21%), SINEs (∼15%), HERVs (∼8%), and other repetitive elements (∼54%). Importantly, transcriptional activation of normally silenced transposable elements, often driven by epigenetic dysregulation such as DNA methylation loss, is a hallmark of cancer. This aberrant activation contributes to malignant transformation and tumor immunogenicity, although the underlying mechanisms remain poorly understood. Notably, HERVs, an important class of repetitive sequences, function as tumor-associated antigens, expressed on the surface of cancer cells, where they influence both innate and adaptive immune responses. The role of HERVs, particularly in early-onset melanoma and prostate cancer (CaP), remains underexplored, especially with respect to prognostication and disease progression. In this study, we investigated the expression and clinical significance of HERV type R (HERV-R) in melanoma and CaP. Using malignant melanoma tissues from Nigeria, benign prostatic samples from African men, and comparative tissues from men of European ancestry in Nigeria and the United Kingdom, we applied transcriptomic and molecular biology techniques to characterize HERV-R activity. Our findings demonstrate marked expression of HERV-R in malignant melanoma, in glandular regions of metastatic CaP tissues, and in both glandular and partially stromal compartments of benign prostatic lesions. These observations suggest that HERV-R holds promise as a prognostic biomarker and potential target for early detection in melanoma and CaP. Furthermore, the consistent glandular expression of HERV-R in both cancerous and benign prostate tissues supports the hypothesis of a mutator phenotype, implicating HERV-R in tumor initiation and progression. Collectively, these results underscore the therapeutic and diagnostic potential of HERV-R and highlight the urgent need for further investigation into HERV-R biology in melanoma and CaP. Citation Format: Faruk Mohammed, Sani Ibrahim, Rebecca Garnham, Ines Hosni, Halimatu Sadiya Musa, Sani Kamarudeen Owolabi, Adoke Kasimu Umar, Jane Carr-Wilkinson, Emma Scott, Ahmad Bello, Kevin Petrie. Genomic transposable elements, repetitive sequences, in early-onset melanoma and prostate cancer among West Africans in Nigeria abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2534.
Mohammed et al. (Fri,) studied this question.