Intrahepatic cholangiocarcinoma (ICC) is a fatal primary liver cancer (PLC) that affects 5-10% of all PLCs. Here we sequence tumour and matching control sample pairs of a large cohort of 103 ICC patients in China, resulting in the identification of an ICC-specific somatic mutational signature that is associated with liver inflammation, fibrosis and cirrhosis. We further uncover 25 significantly mutated genes including eight potential driver genes (TP53, KRAS, IDH1, PTEN, ARID1A, EPPK1, ECE2 and FYN). We find that TP53-defective ICC patients are more likely to be HBsAg-seropositive, whereas mutations in the oncogene KRAS are nearly exclusively found in HBsAg-seronegative ICC patients. Three pathways (Ras/phosphatidylinositol-4,5-bisphosphate 3-kinase signalling, p53/cell cycle signalling and transforming growth factor-beta/Smad signalling), genes important for epigenetic regulation and oxidative phosphorylation are substantially affected in ICC. We reveal mutations in this study that may be valuable for designing further studies, better diagnosis and effective therapies.
[1]Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepatobiliary Med 1, Shanghai 200438, Peoples R China.
[2]Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
[3]Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China.
[4]Wuhan Frasergen Bioinformat Co Ltd, Wuhan 430075, Peoples R China.
[5]Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China.
[6]Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai 200438, Peoples R China.
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