{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:56:51Z","timestamp":1763643411719,"version":"3.40.5"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>B\u2010lymphoblastic leukemia\/lymphoma (B\u2010ALL) is the most common pediatric malignancy and the most commonly diagnosed adult lymphoblastic leukemia. Recent advances have broadened the spectrum of B\u2010ALL, with <jats:italic>DUX4<\/jats:italic> gene fusions implicated in a subclass occurring in adolescents and young adults and harboring a favorable prognosis. <jats:italic>DUX4<\/jats:italic> fusions have been challenging to identify. We aimed to determine whether expression of the DUX4 oncoprotein, as detected by targeted immunohistochemistry, might serve as a surrogate for molecular detection of <jats:italic>DUX4<\/jats:italic> fusions in B\u2010ALL. A cohort of investigational B\u2010ALLs was generated with enrichment for <jats:italic>DUX4<\/jats:italic> fusions by the inclusion of cases with characteristic demographic features and immunophenotypic properties. B\u2010ALLs with mutually exclusive cytogenetics were collected. Immunohistochemical staining by a monoclonal antibody raised against the N\u2010terminus of the DUX4 protein was performed. N\u2010DUX4 immunohistochemistry demonstrated strong, crisp nuclear staining in blasts of seven investigational cases, six of which had nucleic acid material available for molecular evaluation. Five of these cases demonstrated RNA\u2010seq <jats:italic>DUX4\u2010<\/jats:italic>fusion positivity. One N\u2010DUX4 immunohistochemistry positive case lacked a definitive <jats:italic>DUX4\u2010<\/jats:italic>fusion by RNA\u2010seq, though demonstrated a gene expression profile characteristic of <jats:italic>DUX4\u2010<\/jats:italic>rearranged B\u2010ALLs, a CD2+ immunophenotype, and a lack of staining by C\u2010terminus DUX4 antibody immunohistochemistry. At least 83.3% [5\/6] positive predictive value. N\u2010DUX4 immunohistochemistry was negative in blasts of three RNA\u2010seq <jats:italic>DUX4\u2010<\/jats:italic>fusion\u2010negative cases (3\/3; 100% negative predictive value). B\u2010ALLs with mutually exclusive cytogenetic profiles were all N\u2010DUX4 negative (0\/10, specificity 100%). N\u2010DUX4 immunohistochemistry is reliable for the distinction of <jats:italic>DUX4\u2010<\/jats:italic>rearranged B\u2010ALLs from other B\u2010ALLs. We recommend its use for subclassification of B\u2010ALLs in adolescents and young adults and in B\u2010ALLs that remain \u201cnot otherwise specified.\u201d<\/jats:p>","DOI":"10.1002\/gcc.23033","type":"journal-article","created":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T04:39:14Z","timestamp":1645850354000},"page":"449-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["N\u2010terminus <scp>DUX4<\/scp>\u2010immunohistochemistry is a reliable methodology for the diagnosis of <i>DUX4<\/i><i>\u2010<\/i>fused B\u2010lymphoblastic leukemia\/lymphoma (N\u2010terminus <scp>DUX4 IHC<\/scp> for <scp>DUX4<\/scp>\u2010fused <scp>B\u2010ALL<\/scp>)"],"prefix":"10.1002","volume":"61","author":[{"given":"Bradford J.","family":"Siegele","sequence":"first","affiliation":[{"name":"Department of Pathology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"Department of Pathology and Laboratory 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C.","family":"Winters","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Dal Cin","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Treece","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisa","family":"Gaskell","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Nardi","sequence":"additional","affiliation":[{"name":"Department 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