Mutational landscape of intrahepatic cholangiocarcinoma

• Published in: Nature communications Vol. 5; no. 1; p. 5696
• Main Authors: Zou, Shanshan, Li, Jiarui, Zhou, Huabang, Frech, Christian, Jiang, Xiaolan, Chu, Jeffrey S. C., Zhao, Xinyin, Li, Yuqiong, Li, Qiaomei, Wang, Hui, Hu, Jingyi, Kong, Guanyi, Wu, Mengchao, Ding, Chuanfan, Chen, Nansheng, Hu, Heping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.12.2014; Nature Publishing Group
• Subjects: 140/125; 142/126; 631/208/2489/68; 631/208/737; 692/699/1503/1607/1610; Adult; Aged; Bile Duct Neoplasms - genetics; Bile Ducts, Intrahepatic; China; Cholangiocarcinoma - genetics; Cohort Studies; Female; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Isocitrate Dehydrogenase - genetics; Liver Neoplasms - genetics; Male; Middle Aged; multidisciplinary; Mutation; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); PTEN Phosphohydrolase - genetics; ras Proteins - genetics; Science; Science (multidisciplinary); Tumor Suppressor Protein p53 - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6696

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-β/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. Intrahepatic cholangiocarcinoma (ICC) is a fatal primary liver cancer with a known genetic component. Here the authors sequence the exomes of matched tumour and normal tissue from 103 ICC patients in China, and identify an ICC mutational profile associated with liver inflammation, fibrosis and cirrhosis.