Multifocal organoids reveal clonal associations between synchronous intestinal tumors with pervasive heterogeneous drug responses

• DOI: 10.1038/s41525-022-00313-0
• Publication Date: 2022-07-19T18:02:50Z
• Authors: Nahyun Jeong; Soon-Chan Kim; Ji Won Park; Seul Gi Park; Ki-Hoan Nam; Ja Oh Lee; Young-Kyoung Shin; Jeong Mo Bae; Seung-Yong Jeong; Min Jung Kim; Ja-Lok Ku
• Keywords: Organoid; Epigenomics

Multifocal colorectal cancer (CRC) comprises both clonally independent primary tumors caused by inherited predisposition and related mainly due to intraluminal spreading along an intact basement membrane. The distinction between these multifocal CRCs is essential because therapeutic strategies vary according the clonal association of multiple tumor masses. Here, we report one unique case synchronous intestinal (SIC) with occurring entire bowel tract, including small intestine. We established six patient-derived organoids (PDOs), cell lines (PDCs) from each site SIC, which were subjected extensive genomic, transcriptomic, epigenomic sequencing. also estimated drug responses SIC 25 clinically relevant compounds validate how actionable alternations SICs associated sensitivity. Our data demonstrated distinct associations across different organs, consistently supported multi-omics analysis, as well accordant various compounds. results indicated imminent drawback a single tumor-based diagnosis CRC suggested necessity in-depth molecular analysis all regions avoid unexpected resistance currently available targeted therapies.