{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:12:00Z","timestamp":1791619920247,"version":"4.3.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p><jats:italic>ERBB2<\/jats:italic> amplification is one of the most important and mature targets for HER2-targeted drug therapy. Somatic mutations of <jats:italic>ERBB2<\/jats:italic> in the tyrosine kinase domain have been studied extensively, and play a role in response to anti-HER2 therapy among different cancer types. However, <jats:italic>ERBB2<\/jats:italic> fusion has not been got attention and its relevance to HER2-targeted therapy is unclear. We comprehensively characterized <jats:italic>ERBB2<\/jats:italic> fusions from next-generation sequencing (NGS) data between May 2018 and October 2021 in 32,131 various solid tumors. Among the tumors, 0.28% harbored <jats:italic>ERBB2<\/jats:italic> fusions, which occurred more commonly in gastroesophageal junction cancer (3.12%; 3\/96), breast cancer (1.89%; 8\/422), urothelial carcinoma (1.72%; 1\/58), and gastric cancer (1.60%; 23\/1,437). Our population presented with a median age of 65 years (range 28 to 88 years), a high proportion of men (55 men vs 34 women; 61.80%). Among the patients with <jats:italic>ERBB2<\/jats:italic> fusions, <jats:italic>TP53<\/jats:italic> (82%), <jats:italic>APC<\/jats:italic> (18%), and <jats:italic>CDK4<\/jats:italic> (15%) were the top3 co-mutant genes. What\u2019s more, most patients with <jats:italic>ERBB2<\/jats:italic> fusion also had <jats:italic>ERBB2<\/jats:italic> amplification (75.28%; 67\/89), which was similar to the data in the TCGA database (88.00%; 44\/50). Furthermore, TCGA database shows that patients with <jats:italic>ERBB2<\/jats:italic> fusions in pan-cancer had a worse prognosis than those without <jats:italic>ERBB2<\/jats:italic> fusions, as well as in breast cancer. Besides, <jats:italic>ERBB2<\/jats:italic> amplification combined with <jats:italic>ERBB2<\/jats:italic> fusion had worse prognosis than those with only <jats:italic>ERBB2<\/jats:italic> amplification. <jats:italic>ERBB2<\/jats:italic> fusion may interfere the effect of anti-HER2-targeted antibody drugs and influence the prognosis of patients with <jats:italic>ERBB2<\/jats:italic> amplification. Prospective clinical trials are warranted to confirm the results in the future.<\/jats:p>","DOI":"10.3389\/fonc.2022.986674","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T04:31:00Z","timestamp":1665030660000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Molecular and clinicopathological characteristics of ERBB2 gene fusions in 32,131 Chinese patients with solid 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