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Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death with few effective therapies. Patient-derived organoids (PDOs) are a 3-D culture model that allow primary tumour cells to propagate, and have gained considerable traction in many cancer types such as PDAC. However, concerns remain regarding whether these models can predict what occurs in patients. We hypothesize that genomic and transcriptomic drift occurring in PDO models impacts the fidelity of drug response. To investigate, matched WGS and bulk RNAseq was performed on paired PDAC organoids and tumour tissue (n=41). Core biopsies were obtained from in patients with Stage III-IV PDAC enrolled in the COMPASS trial (NCT02750657) and divided for sequencing and organoid generation. Tumour cellularity was enriched by laser capture microdissection. Although alterations in the four major driver genes (KRAS, TP53, SMAD4, CDKN2A) remained consistent, other genomic differences were identified. SNV count was higher in organoids (median 6584 vs 5931, p Citation Format: Irene Y. Xie, Yuanchang Fang, Amy X. Zhang, Karen Ng, Zhen-Mei Liu, Eugenia Flores-Figueroa, Gun Ho Jang, Stephanie Ramotar, Anna Dodd, Julie Wilson, Jennifer J. Knox, Steven Gallinger, Faiyaz Notta. Genomic characterization of patient-derived pancreatic cancer organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 173. |
