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Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma

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dc.contributor.author박영년-
dc.contributor.author이형진-
dc.date.accessioned2018-10-29T16:40:16Z-
dc.date.available2018-10-29T16:40:16Z-
dc.date.issued2017-
dc.identifier.issn2159-8274-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/163848-
dc.description.abstractCholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3' untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores-mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.Significance: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherAmerican Association for Cancer Research-
dc.relation.isPartOfCANCER DISCOVERY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleWhole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pathology (병리학교실)-
dc.contributor.googleauthorApinya Jusakul-
dc.contributor.googleauthorIoana Cutcutache-
dc.contributor.googleauthorChern Han Yong-
dc.contributor.googleauthorJing Quan Lim-
dc.contributor.googleauthorMi Ni Huang-
dc.contributor.googleauthorNisha Padmanabhan-
dc.contributor.googleauthorVishwa Nellore-
dc.contributor.googleauthorSarinya Kongpetch-
dc.contributor.googleauthorAlvin Wei Tian Ng-
dc.contributor.googleauthorLey Moy Ng-
dc.contributor.googleauthorSu Pin Choo-
dc.contributor.googleauthorSwe Swe Myint-
dc.contributor.googleauthorRaynoo Thanan-
dc.contributor.googleauthorSanjanaa Nagarajan-
dc.contributor.googleauthorWeng Khong Lim-
dc.contributor.googleauthorCedric Chuan Young Ng-
dc.contributor.googleauthorArnoud Boot-
dc.contributor.googleauthorMo Liu-
dc.contributor.googleauthorChoon Kiat Ong-
dc.contributor.googleauthorVikneswari Rajasegaran-
dc.contributor.googleauthorStefanus Lie-
dc.contributor.googleauthorAlvin Soon Tiong Lim-
dc.contributor.googleauthorTse Hui Lim-
dc.contributor.googleauthorJing Tan-
dc.contributor.googleauthorJia Liang Loh-
dc.contributor.googleauthorJohn R. McPherson-
dc.contributor.googleauthorNarong Khuntikeo-
dc.contributor.googleauthorVajaraphongsa Bhudhisawasdi-
dc.contributor.googleauthorPuangrat Yongvanit-
dc.contributor.googleauthorSopit Wongkham-
dc.contributor.googleauthorYasushi Totoki-
dc.contributor.googleauthorHiromi Nakamura-
dc.contributor.googleauthorYasuhito Arai-
dc.contributor.googleauthorSatoshi Yamasaki-
dc.contributor.googleauthorPierce Kah-Hoe Chow-
dc.contributor.googleauthorAlexander Yaw Fui Chung-
dc.contributor.googleauthorLondon Lucien Peng Jin Ooi-
dc.contributor.googleauthorKiat Hon Lim-
dc.contributor.googleauthorSimona Dima-
dc.contributor.googleauthorDan G. Duda-
dc.contributor.googleauthorIrinel Popescu-
dc.contributor.googleauthorPhilippe Broet-
dc.contributor.googleauthorSen-Yung Hsieh-
dc.contributor.googleauthorMing-Chin Yu-
dc.contributor.googleauthorAldo Scarpa-
dc.contributor.googleauthorJiaming Lai-
dc.contributor.googleauthorDi-Xian Luo-
dc.contributor.googleauthorAndré Lopes Carvalho-
dc.contributor.googleauthorAndré Luiz Vettore-
dc.contributor.googleauthorHyungjin Rhee-
dc.contributor.googleauthorYoung Nyun Park-
dc.contributor.googleauthorLudmil B. Alexandrov-
dc.contributor.googleauthorRaluca Gordân-
dc.contributor.googleauthorSteven G. Rozen-
dc.contributor.googleauthorTatsuhiro Shibata-
dc.contributor.googleauthorChawalit Pairojkul-
dc.contributor.googleauthorBin Tean Teh-
dc.contributor.googleauthorPatrick Tan-
dc.identifier.doi10.1158/2159-8290.CD-17-0368-
dc.contributor.localIdA01563-
dc.contributor.localIdA01563-
dc.contributor.localIdA05171-
dc.relation.journalcodeJ03328-
dc.identifier.eissn2159-8290-
dc.identifier.pmid28667006-
dc.contributor.alternativeNamePark, Young Nyun-
dc.contributor.alternativeNameRhee, Hyungjin-
dc.contributor.affiliatedAuthor박영년-
dc.contributor.affiliatedAuthor이형진-
dc.citation.volume7-
dc.citation.number10-
dc.citation.startPage1116-
dc.citation.endPage1135-
dc.identifier.bibliographicCitationCANCER DISCOVERY, Vol.7(10) : 1116-1135, 2017-
dc.identifier.rimsid60625-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers

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