Integrative Analysis Defines Distinct Prognostic Subgroups of Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. It is defined by cholangiocytic differentiation and has poor prognosis. Recently, epigenetic processes have been shown to play an important role in cholangiocarcinogenesis. We performed an integrative analysis on 52 iCCAs using both genetic and epigenetic data with a specific focus on DNA methylation components. We identified four major iCCA subgroups with widespread genomic and epigenomic differences and prognostic implications. Furthermore, our data suggest differences in the cell-of-origin of the iCCA subtypes. We conducted genome wide DNA methylation analyses of intrahepatic cholangiocarcinoma (iCCA) and non-neoplastic bile duct.