1. Model for distinct pathways of CCA tumorigenesis.
Model for distinct pathways of CCA tumorigenesis. A proposed model for CCA development in clusters 1 and 4 being driven by distinct mechanisms. Cluster 1 may be initiated by extrinsic carcinogens (fluke-infection) causing genome-wide epigenetic derangement and subsequent spontaneous 5-methylcytosine deamination and CpG>TpG mutations. In contrast, in cluster 4 CCAs, intrinsic genetic mutations in strong driver genes such as IDH1 reflect a primary initiating event and consequently drive DNA hypermethylation. See Discussion for details.
Apinya Jusakul et al. Cancer Discov 2017;7:
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