{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:38:56Z","timestamp":1790959136011,"version":"4.1.0"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precision Oncology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> MET exon 14 skipping alterations ( METex14) comprise a diverse set of actionable oncogene drivers in non\u2013small-cell lung cancer (NSCLC). Recent studies have established the efficacy of tyrosine kinase inhibitors for this patient population. The landscape of co-occurring genetic alterations in METex14 NSCLC and their potential impact to therapeutic sensitivities has not yet been fully described. <\/jats:p><\/jats:sec><jats:sec><jats:title>MATERIALS AND METHODS<\/jats:title><jats:p> METex14 NSCLC cases were collected from three cohorts: the VISION trial, and data sets from Guardant360 and GenePlus. Clinicopathologic characteristics and METex14 mutation sites were analyzed and compared across data sets. Co-occurring genetic alterations and the clonality relationships to METex14 were evaluated. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Of 40,824 NSCLCs, 692 METex14 cases (1.7%) were identified, including 332 in Guardant360, 188 in VISION, and 172 in GenePlus. The demographics and mutation type and\/or sites were similar in the Asian versus Western cohorts. MET amplification, which were found to be associated with sensitivity to MET kinase inhibitors, co-occurs in 7.6%-13.8% of cases, whereas kinase domain secondary mutation of MET co-occurs in 5%-6%. When co-occurring with METex14, EGFR mutations were often identified as the dominant clone (78%, 7 of 9), whereas when co-occurring, METex14 (39%, 7 of 18) and KRAS (44%, 8 of 18) had similar rates of clonal dominance. PIK3CA and PTEN mutations were almost always subclones (89%, 16 of 18) to METex14. Moreover, RET-CCDC6 fusion and EGFR mutation were detected following crizotinib treatment in two patients, suggesting novel mechanisms of resistance. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> METex14 mutations frequently co-occur with other potential driver oncogenes with differing patterns of clonal dominance observed among the drivers. This cellular context can provide insights into whether METex14 is acting as a primary oncogenic driver or resistance mechanism and help guide treatment choices. <\/jats:p><\/jats:sec>","DOI":"10.1200\/po.21.00135","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T20:59:25Z","timestamp":1639429165000},"page":"1802-1812","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Landscape and Clonal Dominance of Co-occurring Genomic Alterations in Non\u2013Small-Cell Lung Cancer Harboring <i>MET<\/i> Exon 14 Skipping"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-1185","authenticated-orcid":false,"given":"Xiuning","family":"Le","sequence":"first","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, 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