25 39

Cited 0 times in

Different mutational characteristics of the subsets of EGFR-tyrosine kinase inhibitor sensitizing mutation-positive lung adenocarcinoma

DC FieldValueLanguage
dc.contributor.author김은영-
dc.contributor.author장윤수-
dc.date.accessioned2019-01-15T17:05:57Z-
dc.date.available2019-01-15T17:05:57Z-
dc.date.issued2018-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/166803-
dc.description.abstractBACKGROUND: A subset of lung adenocarcinoma with EGFR-tyrosine kinase inhibitor sensitizing mutations (mEGFR) is common in non-smokers and women, suggesting that mutational stressors other than smoking are involved. METHODS: Targeted sequencing using a custom panel containing 70 cancer-related genes were performed from 73 cases of lung adenocarcinoma with mEGFR (study cohort). In parallel, publicly available data of 47 TCGA-LUAD cases with mEGFR (LUAD cohort) were extracted from the GDC data portal and analyzed by non-negative matrix factorization using the Maftools package. RESULTS: In the study cohort, the C > A transversions accounted for 12.9% of all single nucleotide variations (SNVs), comprising the second smallest proportion among SNVs. The E19del-subgroup had a significantly lower mutational burden with significantly higher Ti/Tv ratio than the SNV-subgroup, which includes cases with L858R and other EGFR-TKI sensitizing SNVs. (P = 0.0326 and 0.0002, respectively, Mann-Whitney U test). In the LUAD cohort, the mutational burden was substantially lower than in other TCGA cancer cohorts, and the frequency of C > A transversions was 30.3%, occupying the second frequency. The E19del-subgroup had a lower mutational burden overall and a higher Ti/Tv ratio than the SNV-subgroup (P = 0.0497 and P = 0.0055, respectively, Mann-Whitney U test). Smoking-related signature 4 was observed only in the L858R-subgroup, while ignature 30 and 5 was observed in both groups. CONCLUSIONS: Lung adenocarcinoma with mEGFR(+) has a lower mutational burden and does not show a characteristic mutation pattern influenced by smoking. E19del and L858R, which are representative subtypes of mEGFR(+) lung adenocarcinoma, differ in terms of mutational spectrum, as the E19del-subgroup has a lower mutation burden and a higher Ti/Tv ratio than the SNV-subgroup. These findings could help explain the differences in the responses to EGFR-TKIs and in the clinical courses between the two lung adenocarcinoma subgroups.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherBioMed Central-
dc.relation.isPartOfBMC Cancer-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleDifferent mutational characteristics of the subsets of EGFR-tyrosine kinase inhibitor sensitizing mutation-positive lung adenocarcinoma-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorEun Young Kim-
dc.contributor.googleauthorArum Kim-
dc.contributor.googleauthorGaeun Lee-
dc.contributor.googleauthorHangsuck Lee-
dc.contributor.googleauthorYoon Soo Chang-
dc.identifier.doi10.1186/s12885-018-5116-9-
dc.contributor.localIdA00811-
dc.contributor.localIdA03456-
dc.contributor.localIdA03456-
dc.relation.journalcodeJ00351-
dc.identifier.eissn1471-2407-
dc.identifier.pmid30522449-
dc.subject.keywordEGFR-
dc.subject.keywordLung adenocarcinoma-
dc.subject.keywordMutational signatures-
dc.subject.keywordNext-generation sequencing-
dc.subject.keywordSensitizing mutation-
dc.subject.keywordTyrosine kinase inhibitor-
dc.contributor.alternativeNameKim, Eun Young-
dc.contributor.affiliatedAuthor김은영-
dc.contributor.affiliatedAuthor장윤수-
dc.contributor.affiliatedAuthor장윤수-
dc.citation.volume18-
dc.citation.number1-
dc.citation.startPage1221-
dc.identifier.bibliographicCitationBMC Cancer, Vol.18(1) : 1221, 2018-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.