Abstract A005: Detection of fusion oncogenes in routinely collected biorepository samples

Abstract Introduction: A commercial biorepository of tumor samples with associated clinical data is crucial for discovering and validating biomarkers and advancing all stages of cancer research. Although oncogenic fusions are highly specific and attractive drug targets, the progress is limited by their diversity and low (1-4%) prevalence in solid tumors, outside prostate adenocarcinoma (>30% with a characteristic TMPRSS2::ERG fusion). Systematic, cost effective evaluation of banked tumor samples for the oncogenic fusions could accelerate such research efforts. Material and Methods: We examined formalin-fixed paraffin-embedded tumor samples from a commercial biorepository (Reference Medicine, Phoenix, AZ) using a workflow which included expert pathology review, whole slide scanning, construction of multi-tumor tissue microarrays (TMA) immunohistochemistry (IHC) and genomic profiling with commercially available next generation sequencing (NGS) panels. More than 500 tumors were reviewed by board-certified pathologists; selected cases were then cored for TMAs. Immunohistochemistry for ALK and ROS1 proteins' expression were performed on TMAs. Results: IHC for ALK and ROS1 identified two positive cases, one for ROS1 and one for ALK. Thirty eight tumors underwent NGS and both IHC-positive cases were confirmed to harbor gene fusions (EML4::ALK and EZR::ROS1, respectively). All other cases were fusion-negative, concordant with the IHC result. Conclusions: Properly characterized tissue samples are essential for image analysis, biomarker detection and genomic profiling. Rigorous pathologic review helps avoid archiving of poorly preserved samples. IHC screening of TMAs provides a cost-effective approach for identification of fusion events, particularly in non-small cell lung carcinomas, while preserving material for multiple downstream applications. Citation Format: Zoran Gatalica, Inga Rose, Semir Vranic. Detection of fusion oncogenes in routinely collected biorepository samples [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr A005.