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Genetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites

DC Field Value Language
dc.contributor.author김태수-
dc.contributor.author정현철-
dc.contributor.author김효송-
dc.contributor.author박규현-
dc.contributor.author박준용-
dc.contributor.author라선영-
dc.contributor.author권우선-
dc.date.accessioned2017-02-27T08:07:16Z-
dc.date.available2017-02-27T08:07:16Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/147093-
dc.description.abstractPeritoneal carcinomatosis accompanied by malignant ascites is a major cause of death of advanced gastric cancer (GC). To comprehensively characterize the underlying genomic events involved in GC peritoneal carcinomatosis, we analyzed whole-exome sequences of normal gastric tissues, primary tumors, and malignant ascites from eight GC patients. We identified a unique mutational signature biased toward C-to-A substitutions in malignant ascites. In contrast, the patients who received treatment of adjuvant chemotherapy showed a high rate of C-to-T substitutions along with hypermutation in malignant ascites. Comparative analysis revealed several candidate mutations for GC peritoneal carcinomatosis: recurrent mutations in COL4A6, INTS2, and PTPN13; mutations in druggable genes including TEP1, PRKCD, BRAF, ERBB4, PIK3CA, HDAC9, FYN, FASN, BIRC2, FLT3, ROCK1, CD22, and PIK3C2B; and mutations in metastasis-associated genes including TNFSF12, L1CAM, DIAPH3, ROCK1, TGFBR1, MYO9B, NR4A1, and RHOA. Notably, gene ontology analysis revealed the significant enrichment of mutations in the Rho-ROCK signaling pathway-associated biological processes in malignant ascites. At least four of the eight patients acquired somatic mutations in the Rho-ROCK pathway components, suggesting the possible relevance of this pathway to GC peritoneal carcinomatosis. These results provide a genome-wide molecular understanding of GC peritoneal carcinomatosis and its clinical implications, thereby facilitating the development of effective therapeutics.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherImpact Journals-
dc.relation.isPartOfONCOTARGET-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHAscites/genetics*-
dc.subject.MESHBiomarkers, Tumor/genetics*-
dc.subject.MESHCase-Control Studies-
dc.subject.MESHExome/genetics*-
dc.subject.MESHFemale-
dc.subject.MESHFollow-Up Studies-
dc.subject.MESHGenome, Human*-
dc.subject.MESHHigh-Throughput Nucleotide Sequencing/methods-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutation/genetics*-
dc.subject.MESHNeoplasm Staging-
dc.subject.MESHPeritoneal Neoplasms/genetics-
dc.subject.MESHPeritoneal Neoplasms/secondary*-
dc.subject.MESHPrognosis-
dc.subject.MESHRetrospective Studies-
dc.subject.MESHStomach Neoplasms/genetics-
dc.subject.MESHStomach Neoplasms/pathology*-
dc.titleGenetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Internal Medicine-
dc.contributor.googleauthorByungho Lim-
dc.contributor.googleauthorChan Kim-
dc.contributor.googleauthorJeong-Hwan Kim-
dc.contributor.googleauthorWoo Sun Kwon-
dc.contributor.googleauthorWon Seok Lee-
dc.contributor.googleauthorJeong Min Kim-
dc.contributor.googleauthorJun Yong Park-
dc.contributor.googleauthorHyo Song Kim-
dc.contributor.googleauthorKyu Hyun Park-
dc.contributor.googleauthorTae Soo Kim-
dc.contributor.googleauthorJong-Lyul Park-
dc.contributor.googleauthorHyun Cheol Chung-
dc.contributor.googleauthorSun Young Rha-
dc.contributor.googleauthorSeon-Young Kim-
dc.identifier.doi10.18632/oncotarget.6977-
dc.contributor.localIdA04549-
dc.contributor.localIdA03773-
dc.contributor.localIdA01202-
dc.contributor.localIdA04566-
dc.contributor.localIdA01675-
dc.contributor.localIdA01316-
dc.relation.journalcodeJ02421-
dc.identifier.eissn1949-2553-
dc.identifier.pmid26811494-
dc.subject.keywordexome sequencing-
dc.subject.keywordgastric cancer-
dc.subject.keywordmalignant ascites-
dc.subject.keywordperitoneal carcinomatosis-
dc.subject.keywordsomatic mutation-
dc.contributor.alternativeNameKim, Tae Soo-
dc.contributor.alternativeNameChung, Hyun Cheol-
dc.contributor.alternativeNameKim, Hyo Song-
dc.contributor.alternativeNamePark, Kyu Hyun-
dc.contributor.alternativeNamePark, Jun Yong-
dc.contributor.alternativeNameRha, Sun Young-
dc.contributor.affiliatedAuthorKim, Tae Soo-
dc.contributor.affiliatedAuthorChung, Hyun Cheol-
dc.contributor.affiliatedAuthorKim, Hyo Song-
dc.contributor.affiliatedAuthorPark, Kyu Hyun-
dc.contributor.affiliatedAuthorPark, Jun Yong-
dc.contributor.affiliatedAuthorRha, Sun Young-
dc.citation.volume7-
dc.citation.number7-
dc.citation.startPage8055-
dc.citation.endPage8066-
dc.identifier.bibliographicCitationONCOTARGET, Vol.7(7) : 8055-8066, 2016-
dc.date.modified2017-02-24-
dc.identifier.rimsid47125-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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