Abstract A006: Long non-coding RNA Plasmacytoma Variant Translocation 1 Alternative Splicing in Prostate Carcinogenesis

Abstract Prostate cancer remains a major global health concern and disproportionately affects Black men/men of African ancestry (MoAA). Compared to men of European ancestry (MoEA), MoAA experience both a higher incidence of prostate cancer and significantly elevated mortality rates. According to recent American Cancer Society reports, MoAA have a 67% higher incidence of prostate cancer and are more than twice as likely to die from the disease. While socioeconomic and healthcare access factors contribute to these disparities, growing evidence suggests that underlying molecular mechanisms also play a critical role. One emerging molecular factor is the long non-coding RNA Plasmacytoma Variant Translocation 1 (PVT1), which is consistently overexpressed in prostate tumors from MoAA. Prior studies have implicated PVT1 exon 9 in promoting tumor development and progression. Experimental overexpression of exon 9 in prostate cancer models increases tumor aggressiveness and enhances malignant cellular behavior, supporting a functional role in disease severity. In addition, PVT1 exon 9 induces malignant transformation of prostate epithelial cells. However, recent findings indicate that PVT1 is not expressed as a single transcript, but rather as a diverse set of alternatively spliced isoforms, raising the possibility that specific variants may contribute to the observed racial disparities. We hypothesize that a subset of these alternatively spliced PVT1 transcripts is differentially expressed in MoAA and contributes to the increased prostate cancer incidence and mortality observed in this population. To investigate this, we analyzed PVT1 splicing profiles using prostate cancer datasets from two independent studies, including TCGA. We identified ENST00000666076, an alternatively spliced PVT1 transcript located on Chromosome 8: 27,975,972–27,995,613, as being significantly overexpressed in MoAA compared to MoEA. This transcript includes five exons: ENSE00004271579, ENSE00004271636, ENSE00002081483, ENSE00002020395, and ENSE00004271500. In conclusion, our analysis supports emerging reports that distinct PVT1 splice variants may be involved in prostate cancer carcinogenesis. Citation Format: Seidu Adams, Dominique Weatherall, Rachel E. Bonacci, Chinedum C. Udekwu, Olorunseun O. Ogunwobi. Long non-coding RNA Plasmacytoma Variant Translocation 1 Alternative Splicing in Prostate Carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr A006.