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The primary genetic alteration in T\u2010<jats:styled-content style=\"fixed-case\">PLL<\/jats:styled-content> are the inv(14)(q11q32)\/t(14;14)(q11;q32) leading to <jats:styled-content style=\"fixed-case\">TRD<\/jats:styled-content><jats:italic>\/<\/jats:italic><jats:styled-content style=\"fixed-case\">TRA<\/jats:styled-content><jats:italic>\u2010TCL1A<\/jats:italic> fusion, or the t(X;14)(q28;q11) associated with <jats:styled-content style=\"fixed-case\">TRD<\/jats:styled-content><jats:italic>\/<\/jats:italic><jats:styled-content style=\"fixed-case\">TRA<\/jats:styled-content><jats:italic>\u2010<jats:styled-content style=\"fixed-case\">MTCP<\/jats:styled-content>1<\/jats:italic> fusion. However, additional cooperating abnormalities are necessary for emergence of the full neoplastic phenotype. Though the pattern of secondary chromosomal aberrations is remarkably conserved, targets of the changes are largely unknown. We analysed a cohort of 43 well\u2010characterized T\u2010<jats:styled-content style=\"fixed-case\">PLL<\/jats:styled-content> for hotspot mutations in the genes <jats:italic><jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>3, <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>5B<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">RHOA<\/jats:styled-content><\/jats:italic>. Additionally, we selected a subset of 23 T\u2010<jats:styled-content style=\"fixed-case\">PLL<\/jats:styled-content> cases for mutational screening of 54 genes known to be recurrently mutated in T\u2010cell and other haematological neoplasms. Activating mutations in the investigated regions of the <jats:italic><jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>3<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>5B<\/jats:italic> genes were detected in 30% (13\/43) and 21% (8\/39) of the cases, respectively, and were mutually exclusive. Further, we identified mutations in the genes encoding the epigenetic regulators <jats:styled-content style=\"fixed-case\">EZH<\/jats:styled-content>2 in 13% (3\/23), <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>2 in 17% (4\/23) and <jats:styled-content style=\"fixed-case\">BCOR<\/jats:styled-content> in 9% (2\/23) of the cases. We confirmed that the <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content> pathway is a major mutational target, and identified epigenetic regulators recurrently mutated in T\u2010<jats:styled-content style=\"fixed-case\">PLL<\/jats:styled-content>. These findings complement the mutational spectrum of secondary aberrations in T\u2010<jats:styled-content style=\"fixed-case\">PLL<\/jats:styled-content> and underscore the potential therapeutical relevance of epigenetic regulators in T\u2010<jats:styled-content style=\"fixed-case\">PLL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.13952","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T09:01:05Z","timestamp":1456477265000},"page":"265-273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Genes encoding members of the <scp>JAK<\/scp>\u2010<scp>STAT<\/scp> pathway or epigenetic regulators are recurrently mutated in T\u2010cell prolymphocytic leukaemia"],"prefix":"10.1111","volume":"173","author":[{"given":"Cristina","family":"L\u00f3pez","sequence":"first","affiliation":[{"name":"Institute for Human Genetics Christian\u2010Albrechts\u2010University Kiel &amp; University 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