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Genomic and transcriptional alterations of cholangiocarcinoma
Author(s) -
Ito Takeshi,
SakuraiYageta Mika,
Goto Akiteru,
Pairojkul Chawalit,
Yongvanit Puangrat,
Murakami Yoshinori
Publication year - 2014
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1002/jhbp.67
Subject(s) - arid1a , biology , cdkn2a , cancer research , mutation , genetics , gene , bap1 , transcriptome , hepatocellular carcinoma , epigenetics , exome sequencing , bioinformatics , gene expression
Cholangiocarcinoma ( CCA ) is one of the representative cancers refractory to any therapeutic approach. The incidence of CCA is highest in the northeastern part of T hailand, where chronic inflammation caused by liver fluke ( O pisthorchis viverrini: Ov ) infection is a major etiologic factor. The incidence of CCA is also increasing in other countries, including J apan. Here, we overview the genetic and transcriptional alterations of CCA with and without association with Ov infection. CCA with Ov shows enhanced expression of the genes involved in xenobiotic metabolism and chronic inflammatory responses, including cytokine signaling, whereas CCA without Ov shows enhanced expression of growth factor signaling, such as HER2 . Exome and the following prevalence sequencing identified mutations of the BAP1 , ARID1A , IDH1 and IDH2 genes in CCA , in addition to the high incidence of known mutations in the TP53 , KRAS2 SMAD4 , and CDKN2A genes, suggesting the role of chromatin modulators in CCA pathogenesis. CCA with Ov shows significantly higher incidence of the TP53 gene mutation, whereas CCA without Ov showed significantly more frequent mutations of the BAP1 , IDH1 and IDH2 genes. However, CCAs with Ov and without Ov share a similar mutation spectrum dominated by C : G > T : A transitions mainly at CpG dinucleotides, suggesting that CCA shares etiologic factors with pancreatic ductal carcinoma but not with hepatocellular carcinoma. Comprehensive analyses of the genetic and transcriptional alterations of CCA with and without Ov infection would provide useful information for the prevention, early diagnosis, and treatment of CCA .