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Next-generation sequencing reveals somatic mutations that confer exceptional response to everolimus

DC Field Value Language
dc.contributor.author김상우-
dc.contributor.author김현기-
dc.contributor.author김혜련-
dc.contributor.author김효송-
dc.contributor.author박형순-
dc.contributor.author이민구-
dc.contributor.author임선민-
dc.contributor.author정현철-
dc.contributor.author조병철-
dc.contributor.author김소라-
dc.contributor.author양인석-
dc.date.accessioned2017-10-26T07:38:33Z-
dc.date.available2017-10-26T07:38:33Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/152318-
dc.description.abstractBACKGROUND: Given the modest responses to everolimus, a mTOR inhibitor, in multiple tumor types, there is a pressing need to identify predictive biomarkers for this drug. Using targeted ultra-deep sequencing, we aimed to explore genomic alterations that confer extreme sensitivity to everolimus. RESULTS: We collected formalin-fixed paraffin-embedded tumor/normal pairs from 39 patients (22 with exceptional clinical benefit, 17 with no clinical benefit) who were treated with everolimus across various tumor types (13 gastric cancers, 15 renal cell carcinomas, 2 thyroid cancers, 2 head and neck cancer, and 7 sarcomas). Ion AmpliSeqTM Comprehensive Cancer Panel was used to identify alterations across all exons of 409 target genes. Tumors were sequenced to a median coverage of 552x. Cancer genomes are characterized by 219 somatic single-nucleotide variants (181 missense, 9 nonsense, 7 splice-site) and 22 frameshift insertions/deletions, with a median of 2.1 mutations per Mb (0 to 12.4 mutations per Mb). Overall, genomic alterations with activating effect on mTOR signaling were identified in 10 of 22 (45%) patients with clinical benefit and these include MTOR, TSC1, TSC2, NF1, PIK3CA and PIK3CG mutations. Recurrently mutated genes in chromatin remodeling genes (BAP1; n = 2, 12%) and receptor tyrosine kinase signaling (FGFR4; n = 2, 12%) were noted only in patients without clinical benefit. CONCLUSIONS: Regardless of different cancer types, mTOR-pathway-activating mutations confer sensitivity to everolimus. Targeted sequencing of mTOR pathway genes facilitates identification of potential candidates for mTOR inhibitors.-
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.MESHAdenocarcinoma/drug therapy*-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHAged, 80 and over-
dc.subject.MESHAntineoplastic Agents/therapeutic use*-
dc.subject.MESHCarcinoma, Renal Cell/drug therapy-
dc.subject.MESHClass I Phosphatidylinositol 3-Kinases-
dc.subject.MESHClass Ib Phosphatidylinositol 3-Kinase/genetics-
dc.subject.MESHDrug Resistance, Neoplasm/genetics*-
dc.subject.MESHEverolimus/therapeutic use*-
dc.subject.MESHFemale-
dc.subject.MESHHead and Neck Neoplasms/drug therapy-
dc.subject.MESHHigh-Throughput Nucleotide Sequencing-
dc.subject.MESHHumans-
dc.subject.MESHKidney Neoplasms/drug therapy-
dc.subject.MESHLacrimal Apparatus/pathology*-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutation/genetics-
dc.subject.MESHNeurofibromin 1/genetics*-
dc.subject.MESHPhosphatidylinositol 3-Kinases/genetics-
dc.subject.MESHPolymorphism, Single Nucleotide/genetics-
dc.subject.MESHSarcoma/drug therapy-
dc.subject.MESHStomach Neoplasms/drug therapy-
dc.subject.MESHTOR Serine-Threonine Kinases/antagonists & inhibitors-
dc.subject.MESHTOR Serine-Threonine Kinases/genetics*-
dc.subject.MESHThyroid Neoplasms/drug therapy-
dc.subject.MESHTumor Suppressor Protein p53/genetics*-
dc.subject.MESHTumor Suppressor Proteins/genetics-
dc.subject.MESHYoung Adult-
dc.titleNext-generation sequencing reveals somatic mutations that confer exceptional response to everolimus-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Life Science-
dc.contributor.googleauthorSun Min Lim-
dc.contributor.googleauthorHyung Soon Park-
dc.contributor.googleauthorSangwoo Kim-
dc.contributor.googleauthorSora Kim-
dc.contributor.googleauthorSiraj M. Ali-
dc.contributor.googleauthorJoel R. Greenbowe-
dc.contributor.googleauthorIn Seok Yang-
dc.contributor.googleauthorNak-Jung Kwon-
dc.contributor.googleauthorJae Lyun Lee-
dc.contributor.googleauthorMin-Hee Ryu-
dc.contributor.googleauthorJin-Hee Ahn-
dc.contributor.googleauthorJeeyun Lee-
dc.contributor.googleauthorMin Goo Lee-
dc.contributor.googleauthorHyo Song Kim-
dc.contributor.googleauthorHyunki Kim-
dc.contributor.googleauthorHye Ryun Kim-
dc.contributor.googleauthorYong Wha Moon-
dc.contributor.googleauthorHyun Cheol Chung-
dc.contributor.googleauthorJoo-Hang Kim-
dc.contributor.googleauthorYoon-Koo Kang-
dc.contributor.googleauthorByoung Chul Cho-
dc.identifier.doi10.18632/oncotarget.7234-
dc.contributor.localIdA01108-
dc.contributor.localIdA01166-
dc.contributor.localIdA01202-
dc.contributor.localIdA04576-
dc.contributor.localIdA02781-
dc.contributor.localIdA03369-
dc.contributor.localIdA03773-
dc.contributor.localIdA03822-
dc.contributor.localIdA00612-
dc.contributor.localIdA00524-
dc.relation.journalcodeJ02421-
dc.identifier.eissn1949-2553-
dc.identifier.pmid26859683-
dc.subject.keywordNF1-
dc.subject.keywordTSC1-
dc.subject.keywordeverolimus-
dc.subject.keywordmTOR-
dc.subject.keywordnext-generation sequencing-
dc.contributor.alternativeNameKim, Sang Woo-
dc.contributor.alternativeNameKim, Hyun Ki-
dc.contributor.alternativeNameKim, Hye Ryun-
dc.contributor.alternativeNameKim, Hyo Song-
dc.contributor.alternativeNamePark, Hyung Soon-
dc.contributor.alternativeNameLee, Min Goo-
dc.contributor.alternativeNameLim, Sun Min-
dc.contributor.alternativeNameChung, Hyun Cheol-
dc.contributor.alternativeNameCho, Byoung Chul-
dc.contributor.alternativeNameKim, So Ra-
dc.contributor.affiliatedAuthorKim, Hyun Ki-
dc.contributor.affiliatedAuthorKim, Hye Ryun-
dc.contributor.affiliatedAuthorKim, Hyo Song-
dc.contributor.affiliatedAuthorPark, Hyung Soon-
dc.contributor.affiliatedAuthorLee, Min Goo-
dc.contributor.affiliatedAuthorLim, Sun Min-
dc.contributor.affiliatedAuthorChung, Hyun Cheol-
dc.contributor.affiliatedAuthorCho, Byoung Chul-
dc.contributor.affiliatedAuthorKim, So Ra-
dc.contributor.affiliatedAuthorKim, Sang Woo-
dc.citation.volume7-
dc.citation.number9-
dc.citation.startPage10547-
dc.citation.endPage10556-
dc.identifier.bibliographicCitationONCOTARGET , Vol.7(9) : 10547-10556, 2016-
dc.date.modified2017-10-24-
dc.identifier.rimsid48053-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Hospital Medicine (입원의학과) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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