Abstract B017: Spatial proteomic landscape of ovarian clear cell carcinoma with MET fusion transcripts

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Abstract Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with significant relevance in East Asia due to the high incidence rates in Japan, Taiwan, and Singapore. OCCC tumors harbor frequent somatic mutations in ARID1A and PIK3CA with low frequencies in other genomic alterations. However, approximately 20% of early-stage OCCC tumors have been identified to carry fusion transcripts (FTs) in our 10-year retrospective cohort study. In this study, a total of 6 out of 165 early-stage OCCC patients were validated to harbor MET FTs via the Illumina TruSight Oncology 500 HRD panel and nanoString nCounter assays. Formalin fixed paraffin-embedded sections of 10 tumor samples from 6 patients were subjected to spatial profiling by the GeoMx Digital Spatial Profiling (DSP) platform using the IO Proteome Atlas (IPA) panel to cover 570 proteins labeled by IHC-validated human antibodies for immuno-oncology (IO). Areas of illumination (AOIs) were segmented based on PanCK-positive, CD45-positive, and PanCK-negative signals for epithelial, immune, and stromal compartments, respectively. Read counts are quantitated by next generation sequencing (NGS) followed by an in-house pre-processing pipeline of quality control (QC), normalization, and batch effect correction. Unsupervised hierarchical clustering of 257 AOIs revealed 3 distinct clusters of PanCK-positive, CD45-positive, and PanCK-negative segments. Each compartment showed specific pathway activations. Intriguingly, cMet (pY1349) was highly expressed in some but not all PanCK-positive cells from tumors harboring MET TF, suggesting of intra-tumor heterogeneity of c-Met expression. The preliminary findings in this study demonstrate the feasibility to adopt high-plex spatial proteomic profiling to highlight the heterogeneity of OCCC tumors harboring MET FTs. Citation Format: Sydney Rechie Necesario, Thang Truong Le, Ko-Chen Chen, Maria José Carbajal Hernández, Alice Hsiang-Kuo Yang, Wei-Chou Lin, Jung-Ming Cheng, Lin-Hung Wei, Ruby Yun-Ju Huang. Spatial proteomic landscape of ovarian clear cell carcinoma with MET fusion transcripts [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 B017.

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