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

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30522449", "kind": "science-record", "revision": 7, "content_hash": "sha256:cc6abc99cbe438ae0b4beb6de0fde2e4aa86cae4cb801411292081509fac5572", "created_at": "2026-11-01T15:40:39Z", "updated_at": "2026-11-01T22:00:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Different mutational characteristics of the subsets of EGFR-tyrosine kinase inhibitor sensitizing mutation-positive lung adenocarcinoma.", "doi": "10.1186/s12885-018-5116-9", "pmid": "30522449", "authors": ["Eun Young Kim", "Arum Kim", "Gaeun Lee", "Hangsuck Lee", "Yoon Soo Chang"], "journal": "BMC cancer", "year": 2018, "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.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSIONS: 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.", "claims": [{"id": "claim-method", "statement": "The mutation patterns found in cancers are analyzed by non-negative matrix factorization (NMF), and compared to 30 types of mutational signatures [8].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30522449", "locator": "sections[4] \"Statistics\" paragraph 2", "quote": "The mutation patterns found in cancers are analyzed by non-negative matrix factorization (NMF), and compared to 30 types of mutational signatures [8]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All reagents used in this study are commercially available from the listed companies. FFPE tissue blocks can be obtained from the tissue registries of Severance and Gangnam Severance Hospital, which are affiliated hospitals of Yonsei University College of Medicine and can be obtained after IRB evaluation and approval. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30522449", "locator": "sections[19] \"Availability of data and materials\" paragraph 2", "quote": "All reagents used in this study are commercially available from the listed companies. FFPE tissue blocks can be obtained from the tissue registries of Severance and Gangnam Severance Hospital, which are affiliated hospitals of Yonsei University College of Medicine and can be obtained after IRB evaluation and approval. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30522449"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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study cohort according to the VEP", "rows": [["Type of variants", "Number of mutations"], ["Missense", "346"], ["Benign mutations", "127"], ["Modifying", "0"], ["Nonsense", "6"], ["Frameshift", "13"], ["Splicing site", "1"], ["Inframe insertion and deletion", "37"], ["Nonstop mutation", "0"], ["Total", "530"]], "row_count": 10, "column_count": 2, "numeric_cells": 9, "header_rows": 1, "locator": "section[7]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:30522449:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:767e1cb8fcb48318c4a45572f04f22afcc7047d38bc6cfd15cefb7c80729c81d", "bytes": 466, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#Tab3", "version": null, "note": "Classification of variants in LUAD cohort according to the VEP", "structure": {"pmcid": "PMC6282318", "section_index": 9, "section_title": "LUAD cohort has a 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