Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [methylation array]

Approximately 15% of colorectal cancer (CRC) patients present with high levels of microsatellite instability (MSI-H), which is driven by defective mismatch repair (dMMR). While about 20% of MSI-H tumors are associated with the hereditary condition, Lynch syndrome (LS), the majority develop through non-hereditary mechanisms. In recent years, the molecular processes underpinning tumor development in LS patients has been debated, with the longstanding view that dMMR is a secondary process in CRC development of LS patients being questioned. Here, we performed the first multi-omic analysis of normal colon organoids developed from LS and healthy patients to address questions regarding the development of dMMR in LS colon epithelial cells from cancer-free individuals. Illumina EPIC array protocols were performed on healthy and lynch syndrome colon organoids derived from left and right colon at the time of colonoscopy. Pleae note that files from each colon location were processed independently. As such, two processed beta files of differing probe lengths were generated.