Abstract Small-cell neuroendocrine carcinoma (SCNC) is a rare but highly malignant tumor subtype, primarily arising in the lung and prostate. The convergence of SCNCs across diverse tissues enables their identification through conserved SCNC-specific molecular markers, facilitating tumor subtype classification. As a critical post-transcriptional regulatory mechanism, alternative polyadenylation (APA) is involved in various biological processes, especially in tumor progression. However, its role across tumor subtypes remains unclear. Here, we revealed a global 3’UTR lengthening pattern due to APA in the SCNCs. We identified a set of conserved lengthening 3’UTR events across SCNCs originating from different tissues, showing a high association with neural development and related signaling pathways. More broadly, we developed a prediction model using a neural network framework to identify SCNCs based on the SCNC-specific APA signatures as additional molecular markers. Our work provides new insights into the post-transcriptional landscape of SCNCs and establishes APA as a potential biomarker for SCNC identification. Citation Format: Yi Zhang, Xiaofan Zhao, Ya-Mei Hu, Xiao-Xin Sun, Faming Zhao, Nicole Andeen, Rosalie C. Sears, Jonathan R. Brody, Joshi J. Alumkal, Gordon B. Mills, Mushui Dai, Zheng Xia. Global mRNA 3’UTR lengthening in small-cell neuroendocrine carcinoma 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 5929.
Zhang et al. (Fri,) studied this question.