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Nat Commun. 2014 Dec 15;5:5696. doi: 10.1038/ncomms6696.

Mutational landscape of intrahepatic cholangiocarcinoma.

Author information

1
Department of Hepatobiliary Medicine I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
2
1] Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada [2] Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.
3
Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada.
4
Wuhan Frasergen Bioinformatics Co. Ltd, 666 Gaoxin Road, East Lake High-tech Zone, Wuhan 430075, China.
5
School of Medicine, Jiao Tong University, Shanghai 200025, China.
6
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
7
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.

Abstract

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.

PMID:
25526346
DOI:
10.1038/ncomms6696
[Indexed for MEDLINE]

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