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Exome sequencing reveals recurrent REV3L mutations in cisplatin-resistant squamous cell carcinoma of head and neck

DC Field Value Language
dc.contributor.author김상우-
dc.contributor.author김한상-
dc.contributor.author김혜련-
dc.contributor.author조병철-
dc.contributor.author고윤우-
dc.contributor.author최은창-
dc.date.accessioned2017-02-24T07:53:49Z-
dc.date.available2017-02-24T07:53:49Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/146549-
dc.description.abstractDacomitinib, an irreversible pan-HER inhibitor, had shown modest clinical activity in squamous cell carcinoma of head and neck (SCCHN) patients. Therefore, validated predictive biomarkers are required to identify patients most likely to benefit from this therapeutic option. To characterize the genetic landscape of cisplatin-treated SCCHN genomes and identify potential predictive biomarkers for dacomitinib sensitivity, we performed whole exome sequencing on 18 cisplatin-resistant metastatic SCCHN tumors and their matched germline DNA. Platinum-based chemotherapy elevated the mutation rates of SCCHN compared to chemotherapy-naïve SCCHNs. Cisplatin-treated SCCHN genomes uniquely exhibited a novel mutational signature characterized by C:G to A:T transversions at CCR sequence contexts that may have arisen due to error-prone translesional synthesis. Somatic mutations in REV3L, the gene encoding the catalytic subunit of DNA polymerase ζ involved in translesional synthesis, are significantly enriched in a subset of patients who derived extended clinical benefit to dacomitinib (P = 0.04). Functional assays showed that loss-of-function of REV3L dramatically enhanced the sensitivity of SCCHN cells to dacomitinib by the loss of both translesion synthesis and homologous recombination pathways. Our data suggest that the 'platinum' mutational signature and inactivation of REV3L may inform treatment options in patients of recurrent SCCHN.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherNature Publishing Group-
dc.relation.isPartOfSCIENTIFIC REPORTS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHCarcinoma, Squamous Cell/drug therapy-
dc.subject.MESHCarcinoma, Squamous Cell/genetics*-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCisplatin/pharmacology*-
dc.subject.MESHCisplatin/therapeutic use-
dc.subject.MESHDNA Mutational Analysis-
dc.subject.MESHDNA-Binding Proteins/genetics*-
dc.subject.MESHDNA-Directed DNA Polymerase/genetics*-
dc.subject.MESHDrug Resistance, Neoplasm/genetics*-
dc.subject.MESHExome*-
dc.subject.MESHGene Silencing-
dc.subject.MESHHead and Neck Neoplasms/drug therapy-
dc.subject.MESHHead and Neck Neoplasms/genetics*-
dc.subject.MESHHigh-Throughput Nucleotide Sequencing*-
dc.subject.MESHHumans-
dc.subject.MESHMutation*-
dc.subject.MESHQuinazolinones/pharmacology-
dc.subject.MESHQuinazolinones/therapeutic use-
dc.subject.MESHRNA Interference-
dc.subject.MESHRNA, Small Interfering/genetics-
dc.subject.MESHRecombinational DNA Repair-
dc.titleExome sequencing reveals recurrent REV3L mutations in cisplatin-resistant squamous cell carcinoma of head and neck-
dc.typeArticle-
dc.publisher.locationEngland-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Life Science-
dc.contributor.googleauthorKie Kyon Huang-
dc.contributor.googleauthorKangWon Jang-
dc.contributor.googleauthorSangwoo Kim-
dc.contributor.googleauthorHan Sang Kim-
dc.contributor.googleauthorSung-Moo Kim-
dc.contributor.googleauthorHyeong Ju Kwon-
dc.contributor.googleauthorHye Ryun Kim-
dc.contributor.googleauthorHwan Jung Yun-
dc.contributor.googleauthorMyung Ju Ahn-
dc.contributor.googleauthorKeon Uk Park-
dc.contributor.googleauthorKalpana Ramnarayanan-
dc.contributor.googleauthorJohn R. McPherson-
dc.contributor.googleauthorShenliZhang-
dc.contributor.googleauthorJe-Keun Rhee-
dc.contributor.googleauthorAndré L.Vettore-
dc.contributor.googleauthorKakoli Das-
dc.contributor.googleauthorTakatsugu Ishimoto-
dc.contributor.googleauthorJoo Hang Kim-
dc.contributor.googleauthorYoon Woo Koh-
dc.contributor.googleauthorSe Hun Kim-
dc.contributor.googleauthorEun Chang Choi-
dc.contributor.googleauthorBin Tean Teh-
dc.contributor.googleauthorStevenG. Rozen-
dc.contributor.googleauthorTae-Min Kim-
dc.contributor.googleauthorPatrick Tan-
dc.contributor.googleauthorByoung Chul Cho-
dc.identifier.doi10.1038/srep19552-
dc.contributor.localIdA00524-
dc.contributor.localIdA01098-
dc.contributor.localIdA01166-
dc.contributor.localIdA03822-
dc.contributor.localIdA00133-
dc.contributor.localIdA04161-
dc.relation.journalcodeJ02646-
dc.identifier.eissn2045-2322-
dc.identifier.pmid26790612-
dc.contributor.alternativeNameKim, Sang Woo-
dc.contributor.alternativeNameKim, Han Sang-
dc.contributor.alternativeNameKim, Hye Ryun-
dc.contributor.alternativeNameCho, Byoung Chul-
dc.contributor.alternativeNameKoh, Yoon Woo-
dc.contributor.alternativeNameChoi, Eun Chang-
dc.contributor.affiliatedAuthorKim, Sang Woo-
dc.contributor.affiliatedAuthorKim, Han Sang-
dc.contributor.affiliatedAuthorKim, Hye Ryun-
dc.contributor.affiliatedAuthorCho, Byoung Chul-
dc.contributor.affiliatedAuthorKho, Yoon Woo-
dc.contributor.affiliatedAuthorChoi, Eun Chang-
dc.citation.volume6-
dc.citation.startPage19552-
dc.identifier.bibliographicCitationSCIENTIFIC REPORTS, Vol.6 : 19552, 2016-
dc.date.modified2017-02-24-
dc.identifier.rimsid45180-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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