Abstract 2387: Characterizing HERV expression patterns across breast cancer subtypes: Implications for tumor biology and therapeutic targets

Abstract Endogenous Retroviruses (ERVs) are remnants of ancient retroviral infections that have permanently integrated into host genomes, including humans. Human Endogenous Retroviruses (HERVs) are ‘fossil’ viral sequences, having lost their ability to generate infectious viruses due to mutations and deletions accumulated over millions of years. Although most HERVs are deemed non-functional, they constitute up to 8% of the human genome. Some HERVs have roles in gene expression regulation, and others are transcribed under specific conditions, such as in cancer. HERV-K is the most recently integrated class within our genome, with some members retaining relatively intact open reading frames (ORFs), suggesting their potential to encode proteins. In cancer, reactivation of HERV expression may impact gene expression, genomic stability, and cell signaling pathways.In this study, we investigated the expression of HERVs in breast cancer (BC) and non-tumor breast tissue using RNA sequencing (RNA-Seq) data from The Cancer Genome Atlas (TCGA). Specifically, we analyzed the expression profiles of HERVs across BC subgroups and their association with protein-coding gene expression profiles. We identified differentially expressed HERVs in BC subgroups (HR-/HER2-, HR+/HER2+, HR-/HER2+, HR+/HER2-) in comparison to non-tumor samples. Our analysis revealed 98 differentially expressed HERVs in HR-/HER2-, 51 in HR+/HER2+, 81 in HR-/HER2+, and 48 in HR+/HER2-. Distinct expression profiles across all subtypes were evident. Furthermore, we identified 45 differentially expressed protein-coding genes with transcription start sites within 5 kb of differentially expressed HERVs. This proximity suggests a potential regulatory influence of HERVs on these genes, indicating the need for further research to clarify the underlying mechanisms. In conclusion, the unique HERV expression profiles across BC subtypes suggest specific molecular characteristics and gene regulation patterns. These findings may aid in identifying new therapeutic targets and treatment strategies for breast cancer, emphasizing HERVs' importance in tumor biology. Citation Format: Nathália Da Roz D'Alessandre, Gabriela Der Agopian Guardia, Helena Beatriz da Conceição, Rafael Loch Batista, Pedro Alexandre Favoretto Galante. Characterizing HERV expression patterns across breast cancer subtypes: Implications for tumor biology and therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2387.