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In addition, targeting MET with monoclonal antibodies or tyrosine kinase inhibitors had limited success. We searched for additional genetic alterations that might explain the poor outcome of MET\u2010positive GC and lack of response to MET\u2010targeted therapies. Multiregional whole\u2010exome sequencing was performed on primary tumor and lymph node metastasis samples from two\n                    <jats:italic>MET<\/jats:italic>\n                    \u2010amplified discovery cases. Immunohistochemistry,\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization, and digital droplet polymerase chain reaction were performed in a validation cohort of 24\n                    <jats:italic>MET<\/jats:italic>\n                    \u2010amplified GCs. Whole\u2010exome sequencing found 191 and 166 non\u2010synonymous mutations, respectively. Only eight genes showed non\u2010synonymous mutations in both cases, including\n                    <jats:italic>TP53<\/jats:italic>\n                    . Copy number variations (CNVs) were found in 18 and 14 autosomes, respectively, most commonly affecting chromosome 7. Since\n                    <jats:italic>BRAF<\/jats:italic>\n                    ,\n                    <jats:italic>CDK6<\/jats:italic>\n                    , and\n                    <jats:italic>EGFR<\/jats:italic>\n                    are also localized on chromosome 7, validation studies were performed by fluorescence or chromogenic\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization, and co\u2010amplification was found in 54% of the cases, including two discovery and 24 validation cases. Different combinations were found, for example,\n                    <jats:italic>CDK6\u2009+\u2009MET<\/jats:italic>\n                    ,\n                    <jats:italic>EGFR\u2009+\u2009MET<\/jats:italic>\n                    ,\n                    <jats:italic>CDK6\u2009+\u2009EGFR\u2009+\u2009MET<\/jats:italic>\n                    ,\n                    <jats:italic>BRAF\u2009+\u2009CDK6\u2009+\u2009EGFR\u2009+\u2009MET<\/jats:italic>\n                    , or\n                    <jats:italic>BRAF\u2009+\u2009EGFR\u2009+\u2009MET<\/jats:italic>\n                    . A database search using cBioPortal confirmed our findings. However, marked intra\u2010 and intertumoral heterogeneity was observed, and CNVs were highly variable and spatially separated.\n                    <jats:italic>MET<\/jats:italic>\n                    amplification in GC is accompanied by amplification of other oncogenes located on chromosome 7, that is,\n                    <jats:italic>BRAF<\/jats:italic>\n                    ,\n                    <jats:italic>CDK6<\/jats:italic>\n                    , and\n                    <jats:italic>EGFR<\/jats:italic>\n                    , in a highly heterogeneous manner leading to substantial intra\u2010 and intertumoral heterogeneity. This may cause diagnostic and therapeutic challenges, provoke subclonal evolution, and lead to poor prognosis of\n                    <jats:italic>MET<\/jats:italic>\n                    \u2010amplified GC and the failure of targeted therapies.\n                  <\/jats:p>","DOI":"10.1002\/2056-4538.70104","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:05:54Z","timestamp":1783505154000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>MET<\/i>\n                    <\/scp>\n                    \u2010amplified gastric cancers exhibit co\u2010amplifications of\n                    <scp>\n                      <i>BRAF<\/i>\n                    <\/scp>\n                    ,\n                    <scp>\n                      <i>CDK6<\/i>\n                    <\/scp>\n                    , and\n                    <scp>\n                      <i>EGFR<\/i>\n                    <\/scp>"],"prefix":"10.1002","volume":"12","author":[{"given":"Silke","family":"L\u00fcschen","sequence":"first","affiliation":[{"name":"Department of Pathology University Hospital Schleswig\u2010Holstein (UKSH), Campus Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Ebert","sequence":"additional","affiliation":[{"name":"Department of Pathology University Hospital Schleswig\u2010Holstein (UKSH), Campus Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Michael","family":"Behrens","sequence":"additional","affiliation":[{"name":"Department of Pathology University Hospital Schleswig\u2010Holstein (UKSH), Campus Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-7600","authenticated-orcid":false,"given":"Sandra","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Department 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Hematology and Oncology University Hospital Schleswig\u2010Holstein (UKSH), Campus Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Visceral, Thoracic, Transplantation and Pediatric Surgery University Hospital Schleswig\u2010Holstein (UKSH), Campus Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9692-8828","authenticated-orcid":false,"given":"Philip","family":"Rosenstiel","sequence":"additional","affiliation":[{"name":"Institute for Clinical Molecular Biology Christian\u2010Albrechts\u2010University  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9680-7153","authenticated-orcid":false,"given":"Tobias","family":"Mei\u00dfner","sequence":"additional","affiliation":[{"name":"Department of Cancer Genomics Avera Cancer 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