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We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub\u2010entities proved unfavorable for survival. Within the prospectively registered, population\u2010based German\/Swiss SIOP\u2010LGG 2004 cohort 100 patients (age 0.8\u201017.8\u2009years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19\/35 patients. Five years event\u2010free survival dropped to 0.44, while 5\u2009years overall survival was 0.90 (median observation time 8.3\u2009years). Extensive genetic profiling of 65\/100 DG2 identified\n                    <jats:italic>Histone3\u2010K27M<\/jats:italic>\n                    \u2010mutation in 4,\n                    <jats:italic>IDH1<\/jats:italic>\n                    \u2010mutation in 11,\n                    <jats:italic>BRAF\u2010V600<\/jats:italic>\n                    \u2010mutation in 12,\n                    <jats:italic>KIAA1549\u2010BRAF<\/jats:italic>\n                    \u2010fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8\u2009years, except for tumors carrying\n                    <jats:italic>KIAA1549\u2010BRAF<\/jats:italic>\n                    \u2010fusions.\n                    <jats:italic>Histone3\u2010K27M<\/jats:italic>\n                    \u2010mutant tumors proved uniformly fatal within 0.6 to 2.4\u2009years. The current LGG treatment strategy seems appropriate for all DG2\u2010entities, with the exemption of\n                    <jats:italic>Histone3\u2010K27M<\/jats:italic>\n                    \u2010mutant tumors that require a HGG\u2010related treatment strategy. Our data confirm the importance to genetically define pediatric low\u2010grade diffuse gliomas for proper treatment decisions and risk assessment.\n                  <\/jats:p>","DOI":"10.1002\/ijc.32995","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T06:27:55Z","timestamp":1585808875000},"page":"2159-2175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Prognostic impact of distinct genetic entities in pediatric diffuse glioma\n                    <scp>WHO<\/scp>\n                    \u2010grade\n                    <scp>II<\/scp>\n                    \u2014Report from the German\/Swiss\n                    <scp>SIOP\u2010LGG<\/scp>\n                    2004 cohort"],"prefix":"10.1002","volume":"147","author":[{"given":"Fabian","family":"Falkenstein","sequence":"first","affiliation":[{"name":"Swabian Children's Cancer Center University Hospital Augsburg  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gessi","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, DGNN Brain Tumor Reference Center University of Bonn  Bonn Germany"},{"name":"Division of Pathology Fondazione Policlinico Universitario \u201cA.Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Kandels","sequence":"additional","affiliation":[{"name":"Swabian Children's Cancer Center University Hospital Augsburg  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho\u2010Keung","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology The Chinese University of Hong Kong  Shatin Hong 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf\u2010Dieter","family":"Kortmann","sequence":"additional","affiliation":[{"name":"Department of Radio\u2010Oncology University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Timmermann","sequence":"additional","affiliation":[{"name":"Department of Particle Therapy University Hospital Essen, West German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), German Cancer Consortium (DKTK)  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich\u2010Wilhelm","family":"Thomale","sequence":"additional","affiliation":[{"name":"Pediatric Neurosurgery Charit\u00e9 Universitaetsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Albert","sequence":"additional","affiliation":[{"name":"Dr von Hauner Children's Hospital Ludwig\u2010Maximilians 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