{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:04:47Z","timestamp":1790255087238,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    NOTCH signaling is activated in tumors through multiple mechanisms, including mutations, gene rearrangements, and gene amplification. We report a novel activation mechanism, an internal tandem duplication (ITD) near the NOTCH3 negative regulatory region (NRR), found in a myogenic mesenchymal neoplasm. This 17\u2010amino acid residue duplication disrupts the tightly autoinhibited structure surrounding the S2 cleavage site, resulting in ligand\u2010independent S2 cleavage and constitutive pathway activation, as demonstrated by increased expression of the NOTCH3 target gene\n                    <jats:italic>HES1<\/jats:italic>\n                    . Cells expressing NOTCH3\u2010ITD showed increased nuclear localization of the receptor and exhibited malignant phenotypes, including enhanced proliferation and migration. Together, these findings support the oncogenic role of NOTCH3\u2010ITD.\n                  <\/jats:p>","DOI":"10.1002\/gcc.70169","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:08:43Z","timestamp":1788779323000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>NOTCH3<\/i>\n                    <\/scp>\n                    Internal Tandem Duplication Defines a Novel Oncogenic Activation Mechanism of\n                    <scp>NOTCH<\/scp>\n                    Signaling"],"prefix":"10.1002","volume":"65","author":[{"given":"Hongyi","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pathology Guangdong Women and Children Hospital  Guangzhou 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