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Targeted sequencing identifies genetic alterations that confer primary resistance to EGFR tyrosine kinase inhibitor (Korean Lung Cancer Consortium)

DC Field Value Language
dc.contributor.author김혜련-
dc.contributor.author임선민-
dc.contributor.author조병철-
dc.date.accessioned2017-10-26T07:28:46Z-
dc.date.available2017-10-26T07:28:46Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/152084-
dc.description.abstractBACKGROUND: Non-small-cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations may exhibit primary resistance to EGFR tyrosine kinase inhibitor (TKI). We aimed to examine genomic alterations associated with de novo resistance to gefitinib in a prospective study of NSCLC patients. Patients and methods: One-hundred and fifty two patients with activating EGFR mutations were included in this study and 136 patients' tumor sample were available for targeted sequencing of genomic alterations in 22 genes using the Colon and Lung Cancer panel (Ampliseq, Life Technologies). Results: All 132 patients with EGFR mutation were treated with gefitinib for their treatment of advanced NSCLC. Twenty patients showed primary resistance to EGFR TKI, and were classified as non-responders. A total of 543 somatic single-nucleotide variants (498 missense, 13 nonsense) and 32 frameshift insertions/deletions, with a median of 3 mutations per sample. TP53 was most commonly mutated (47%) and mutations in SMAD4 was also common (19%), as well as DDR2 (16%), PIK3CA (15%), STK11 (14%), and BRAF (7%). Genomic mutations in the PI3K/Akt/mTOR pathway were commonly found in non-responders (45%) compared to responders (27%), and they had significantly shorter progression-free survival and overall survival compared to patients without mutations (2.1 vs. 12.8 months, P=0.04, 15.7 vs. not reached, P<0.001). FGFR 1-3 alterations, KRAS mutations and TP53 mutations were more commonly detected in non-responders compared to responders. Conclusions: Genomic mutations in the PI3K/Akt/mTOR pathway were commonly identified in non-responders and may confer resistance to EGFR TKI. Screening lung adenocarcinoma patients with clinical cancer gene test may aid in selecting out those who show primary resistance to EGFR TKI (NCT01697163).-
dc.description.statementOfResponsibilityopen-
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.MESHAged, 80 and over-
dc.subject.MESHCarcinoma, Non-Small-Cell Lung/drug therapy-
dc.subject.MESHCarcinoma, Non-Small-Cell Lung/genetics*-
dc.subject.MESHCarcinoma, Non-Small-Cell Lung/pathology-
dc.subject.MESHDrug Resistance, Neoplasm/genetics*-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHKaplan-Meier Estimate-
dc.subject.MESHLung Neoplasms/drug therapy-
dc.subject.MESHLung Neoplasms/genetics*-
dc.subject.MESHLung Neoplasms/pathology-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutation*-
dc.subject.MESHProspective Studies-
dc.subject.MESHProtein Kinase Inhibitors/pharmacology*-
dc.subject.MESHProtein Kinase Inhibitors/therapeutic use-
dc.subject.MESHQuinazolines/pharmacology-
dc.subject.MESHReceptor, Epidermal Growth Factor/antagonists & inhibitors*-
dc.subject.MESHReceptor, Epidermal Growth Factor/genetics-
dc.subject.MESHSequence Analysis, DNA/methods-
dc.subject.MESHTreatment Outcome-
dc.titleTargeted sequencing identifies genetic alterations that confer primary resistance to EGFR tyrosine kinase inhibitor (Korean Lung Cancer Consortium)-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Internal Medicine-
dc.contributor.googleauthorSun Min Lim-
dc.contributor.googleauthorHye Ryun Kim-
dc.contributor.googleauthorEun Kyung Cho-
dc.contributor.googleauthorYoung Joo Min-
dc.contributor.googleauthorJin Seok Ahn-
dc.contributor.googleauthorMyung-Ju Ahn-
dc.contributor.googleauthorKeunchil Park-
dc.contributor.googleauthorByoung Chul Cho-
dc.contributor.googleauthorJi-Hyun Lee-
dc.contributor.googleauthorHye Cheol Jeong-
dc.contributor.googleauthorEun Kyung Kim-
dc.contributor.googleauthorJoo-Hang Kim-
dc.identifier.doi10.18632/oncotarget.8904-
dc.contributor.localIdA03369-
dc.contributor.localIdA03822-
dc.contributor.localIdA01166-
dc.relation.journalcodeJ02421-
dc.identifier.eissn1949-2553-
dc.identifier.pmid27121209-
dc.subject.keywordepidermal growth factor-
dc.subject.keywordnext-generation sequencing-
dc.subject.keywordprimary resistance-
dc.subject.keywordtyrosine kinase inhibitor-
dc.contributor.alternativeNameKim, Hye Ryun-
dc.contributor.alternativeNameLim, Sun Min-
dc.contributor.alternativeNameCho, Byoung Chul-
dc.contributor.affiliatedAuthorLim, Sun Min-
dc.contributor.affiliatedAuthorCho, Byoung Chul-
dc.contributor.affiliatedAuthorKim, Hye Ryun-
dc.citation.volume7-
dc.citation.number24-
dc.citation.startPage36311-
dc.citation.endPage36320-
dc.identifier.bibliographicCitationONCOTARGET , Vol.7(24) : 36311-36320, 2016-
dc.date.modified2017-10-24-
dc.identifier.rimsid46864-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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