DRP003579
Exome sequencing of iPSC-like cell lines derived from colon tumors in Apc min mouse model
Genotype-linked disease phenotypes are often observed in an organ-specific manner, suggesting that the correlation between the genotype and phenotype depends on the cell type. However, there is limited direct evidence on the cell type-specific correlation between the genotype and phenotype. Induced pluripotent stem cells (iPSCs), the generation of which enables the control of cell fate while retaining the original genetic information, are suitable for investigating the cell type-specific correlation between the genotype and phenotype. By establishing iPSCs from neoplastic cells, we can obtain various cell types that share genetic information associated with tumor development. The APC gene was initially discovered as a mutated gene in patients with familial adenomatous polyposis and somatic APC mutations are found in the majority of sporadic colon cancers. However, with the exception of the intestinal cell lineage, the consequences of Apc mutations have not been fully elucidated in most cell types.  Here, we established seven iPSC-like cell lines from colon tumor cells in Apc min/+ mouse model. Then, we performed exome sequencing for them to examine their genetic status including Apc gene. By utilizing iPSC-like cell lines which harbor Apc LOH or additional Apc mutations (reprogrammed colon tumor cells: RTCs), we investigated the impact of the cellular context on the consequence of Apc mutations and showed the divergent in vivo consequences of Apc mutation that arise in different cellular contexts.