{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:15:30Z","timestamp":1791152130955,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T00:00:00Z","timestamp":1358899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>T\u2010cell acute lymphoblastic leukemia (T\u2010ALL) is an aggressive and heterogeneous disease. The diagnosis is predominantly based on immunophenotyping. In addition to known cytogenetic abnormalities molecular mutations were recently identified. Here, 90 adult T\u2010ALL cases were investigated for mutations in <jats:italic>NOTCH1<\/jats:italic>, <jats:italic>FBXW7<\/jats:italic>, <jats:italic>PHF6<\/jats:italic>, <jats:italic>CDKN2A, DNMT3A<\/jats:italic>, <jats:italic>FLT3<\/jats:italic>, <jats:italic>PTEN<\/jats:italic>, and <jats:italic>RUNX1<\/jats:italic> using 454 next\u2010generation amplicon sequencing and melting curve analyses. These data were further complemented by FISH, chromosome banding, array CGH, and <jats:italic>CDKN2B<\/jats:italic> promoter methylation analyses. <jats:italic>NOTCH1<\/jats:italic> was the most frequently mutated gene with a 71.1% frequency followed by <jats:italic>FBXW7<\/jats:italic> (18.9%), <jats:italic>PHF6<\/jats:italic> (39.5%), <jats:italic>DNMT3A<\/jats:italic> (17.8%), <jats:italic>RUNX1<\/jats:italic> (15.5%), <jats:italic>PTEN<\/jats:italic> (10.0%), <jats:italic>CDKN2A<\/jats:italic> (4.4%), <jats:italic>FLT3<\/jats:italic>\u2010ITD (2.2%), and <jats:italic>FLT3<\/jats:italic>\u2010TKD (1.1%). In total, 84\/90 (93.3%) cases harbored at least one mutation. Combining these data with <jats:italic>CDKN2A\/B<\/jats:italic> deletions and <jats:italic>CDKN2B<\/jats:italic> methylation status, we detected minimum one aberration in 89\/90 (98.9%) patients. Survival analyses revealed the subtype as defined by the immunophenotype as the strongest independent prognostic factor. When restricting the survival analysis to the early T\u2010ALL subtype, a strong association of <jats:italic>RUNX1<\/jats:italic> (<jats:italic>P<\/jats:italic> = 0.027) and <jats:italic>DNMT3A<\/jats:italic> (<jats:italic>P<\/jats:italic> = 0.005) mutations with shorter overall survival was observed. In conclusion, <jats:italic>RUNX1<\/jats:italic> and <jats:italic>DNMT3A<\/jats:italic> are frequently mutated in T\u2010ALL and are associated with poor prognosis in early T\u2010ALL. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22039","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T12:34:44Z","timestamp":1358944484000},"page":"410-422","source":"Crossref","is-referenced-by-count":145,"title":["The molecular profile of adult T\u2010cell acute lymphoblastic leukemia: Mutations in <i>RUNX1<\/i> and <i>DNMT3A<\/i> are associated with poor prognosis in T\u2010ALL"],"prefix":"10.1002","volume":"52","author":[{"given":"Vera","family":"Grossmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Haferlach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Weissmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Roller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Schindela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Poetzinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Stadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Bellos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Haferlach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Schnittger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kohlmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,23]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-184069"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.5253"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2010.02.001"},{"key":"e_1_2_5_6_1","first-page":"1783","article-title":"Proposals for the immunological classification of acute leukemias. 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