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dc.contributor.author황승용-
dc.date.accessioned2018-02-12T07:17:38Z-
dc.date.available2018-02-12T07:17:38Z-
dc.date.issued2016-03-
dc.identifier.citationCANCER BIOLOGY & THERAPY, v. 17, NO 3, Page. 237-245en_US
dc.identifier.issn1538-4047-
dc.identifier.issn1555-8576-
dc.identifier.urihttp://www.tandfonline.com/doi/full/10.1080/15384047.2016.1139235-
dc.identifier.urihttp://hdl.handle.net/20.500.11754/36811-
dc.description.abstractCompound EGFR mutations, defined as double or multiple mutations in the EGFR tyrosine kinase domain, are frequently detected with advances in sequencing technology but its clinical significance is unclear. This study analyzed 61 cases of EGFR mutation positive lung adenocarcinoma using next-generation sequencing (NGS) based repeated deep sequencing panel of 16 genes that contain actionable mutations and investigated clinical implication of compound EGFR mutations. Compound EGFR mutation was detected in 15 (24.6%) of 61 cases of EGFR mutation-positive lung adenocarcinoma. The majority (12/15) of compound mutations are combination of the atypical mutation and typical mutations such as exon19 deletion, L858R or G719X substitutions, or exon 20 insertion whereas 3 were combinations of rare atypical mutations. The patients with compound mutation showed shorter overall survival than those with simple mutations (83.7 vs. 72.8 mo; P = 0.020, Breslow test). Among the 115 missense mutations discovered in the tested genes, a few number of actionable mutations were detected irrelevant to the subtype of EGFR mutations, including ALK rearrangement, BCL2L11 intron 2 deletion, KRAS c.35G>A, PIK3CA c.1633G>A which are possible target of crizotinib, BH3 mimetics, MEK inhibitors, and PI3K-tyrosine kinase inhibitors, respectively. 31 missense mutations were detected in the cases with simple mutations whereas 84 in those with compound mutation, showing that the cases with compound missense mutation have higher burden of missense mutations (P = 0.001, independent sample t-test). Compound EGFR mutations are detected at a high frequency using NGS-based repeated deep sequencing. Because patients with compound EGFR mutations showed poor clinical outcomes, they should be closely monitored during follow-up.en_US
dc.description.sponsorshipThis study was supported by an NSCR grant (HI10C2020) awarded to YS Chang.en_US
dc.language.isoenen_US
dc.publisherTAYLOR & FRANCIS INCen_US
dc.subjectCompound EGFR mutationen_US
dc.subjectco-mutationen_US
dc.subjectEGFRen_US
dc.subjectlung adenocarcinomaen_US
dc.subjectNGSen_US
dc.subjectrepeated deep sequencingen_US
dc.subjectsimple EGFR mutationen_US
dc.titleCompound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinomaen_US
dc.typeArticleen_US
dc.relation.no3-
dc.relation.volume17-
dc.identifier.doi10.1080/15384047.2016.1139235-
dc.relation.page237-245-
dc.relation.journalCANCER BIOLOGY & THERAPY-
dc.contributor.googleauthorKim, Eun Young-
dc.contributor.googleauthorCho, Eun Na-
dc.contributor.googleauthorPark, Heae Surng-
dc.contributor.googleauthorHong, Ji Young-
dc.contributor.googleauthorLim, Seri-
dc.contributor.googleauthorYoun, Jong Pil-
dc.contributor.googleauthorHwang, Seung Yong-
dc.contributor.googleauthorChang, Yoon Soo-
dc.relation.code2016004841-
dc.sector.campusS-
dc.sector.daehakGRADUATE SCHOOL[S]-
dc.sector.departmentDEPARTMENT OF BIONANOTECHNOLOGY-
dc.identifier.pidsyhwang-


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