title: Pathogenesis of cholangiocarcinoma: From genetics to signalling pathways.
abstract: Cholangiocarcinoma (CCA) is a malignant tumour of bile duct epithelial cells with dismal prognosis and rising incidence. Chronic inflammation resulting from liver fluke infection, hepatitis and other inflammatory bowel diseases is a major contributing factor to cholangiocarcinogenesis, likely through accumulation of serial genetic and epigenetic alterations resulting in aberration of oncogenes and tumour suppressors. Recent studies making use of advances in high-throughput genomics have revealed the genetic landscape of CCA, greatly increasing our understanding of its underlying biology. A series of highly recurrent mutations in genes such as TP53, KRAS, SMAD4, BRAF, MLL3, ARID1A, PBRM1 and BAP1, which are known to be involved in cell cycle control, cell signalling pathways and chromatin dynamics, have led to investigations of their roles, through molecular to mouse modelling studies, in cholangiocarcinogenesis. This review focuses on the landscape genetic alterations in CCA and its functional relevance to the formation and progression of CCA.
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore; Department of Pharmacology, Faculty of Medicine and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, Thailand; Division of Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore. Electronic address: sarinya.kongpetch@nccs.com.sg.
authors.forename: Sarinya
authors.initials: S
authors.lastname: Kongpetch
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore; Division of Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore. Electronic address: apinya.jusakul@duke-nus.edu.sg.
authors.forename: Apinya
authors.initials: A
authors.lastname: Jusakul
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore; Division of Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore. Electronic address: cmrock@nccs.com.sg.
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore; Division of Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore. Electronic address: wengkhong.lim@duke-nus.edu.sg.
authors.forename: Weng Khong
authors.initials: WK
authors.lastname: Lim
authors.affiliation: Division of Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore; Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore. Electronic address: steve.rozen@duke-nus.edu.sg.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Rozen
authors.affiliation: Division of Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore; Genome Institute of Singapore, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore. Electronic address: gmstanp@duke-nus.edu.sg.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore; Division of Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore. Electronic address: teh.bin.tean@singhealth.com.sg.
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015398:Signal Transduction / Q000235:genetics*
keywords: Cholangiocarcinoma; Chromatin; Genetic alteration; Molecular pathogenesis