EP011/#648 Development and genomic characterization of patient-derived endometrial cancer organoids. (4th December 2022)

• Record Type: Journal Article
• Authors: Kim, Mi-Kyung; Kim, Bora; Kim, Yun Hwan; Ku, Ja-Lok
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 3
• Page Start: A53
• Page End: A53
• Publication Date: 2022-12-04
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-igcs.102
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objectives: We have developed endometrial cancer organoids to establish reliable pre-clinical models, and performed genomic characterization of the established organoids to assess whether they maintain the mutational landscapes of the original tumors from which the organoids originated. Methods: Endometrial cancer organoids were cultured using endometrial cancer surgical specimens. After establishment of the organoids, we performed whole genome sequencing (WGS) on original tumor tissues and the paired organoids to identify driver mutations, mutational signatures, and structural variations. We also classified the organoids based on the TCGA molecular classifications. Results: Endometrial cancer organoids were successfully established in 7 of 34 cases (20%) and 11 cases (32%) are ongoing. Among them, we performed WGS analysis on 5 pairs of original endometrial cancer tissue and organoid. Although numerous passenger mutations were accumulated during organoid culture, all the established organoids retained the driver mutations of the tumors and showed similar mutational signatures. The organoids comprised the 4 TCGA molecular classifications, including 1 POLE ultramutated, 1 MSI (MSH6 mutation), 1 TP53 mutated, and 2 copy-number low groups. Conclusions: We developed endometrial cancer organoids representing the 4 TCGA molecular classifications, which will provide useful experimental models for translational research.