Cited 9 times in
Different mutational characteristics of the subsets of EGFR-tyrosine kinase inhibitor sensitizing mutation-positive lung adenocarcinoma
DC Field | Value | Language |
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dc.contributor.author | 김은영 | - |
dc.contributor.author | 장윤수 | - |
dc.date.accessioned | 2019-01-15T17:05:57Z | - |
dc.date.available | 2019-01-15T17:05:57Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/166803 | - |
dc.description.abstract | BACKGROUND: 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.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | BioMed Central | - |
dc.relation.isPartOf | BMC CANCER | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Different mutational characteristics of the subsets of EGFR-tyrosine kinase inhibitor sensitizing mutation-positive lung adenocarcinoma | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Eun Young Kim | - |
dc.contributor.googleauthor | Arum Kim | - |
dc.contributor.googleauthor | Gaeun Lee | - |
dc.contributor.googleauthor | Hangsuck Lee | - |
dc.contributor.googleauthor | Yoon Soo Chang | - |
dc.identifier.doi | 10.1186/s12885-018-5116-9 | - |
dc.contributor.localId | A00811 | - |
dc.contributor.localId | A03456 | - |
dc.relation.journalcode | J00351 | - |
dc.identifier.eissn | 1471-2407 | - |
dc.identifier.pmid | 30522449 | - |
dc.subject.keyword | EGFR | - |
dc.subject.keyword | Lung adenocarcinoma | - |
dc.subject.keyword | Mutational signatures | - |
dc.subject.keyword | Next-generation sequencing | - |
dc.subject.keyword | Sensitizing mutation | - |
dc.subject.keyword | Tyrosine kinase inhibitor | - |
dc.contributor.alternativeName | Kim, Eun Young | - |
dc.contributor.affiliatedAuthor | 김은영 | - |
dc.contributor.affiliatedAuthor | 장윤수 | - |
dc.citation.volume | 18 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 1221 | - |
dc.identifier.bibliographicCitation | BMC CANCER, Vol.18(1) : 1221, 2018 | - |
dc.identifier.rimsid | 58180 | - |
dc.type.rims | ART | - |
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