Yasuki Suruga1, Kaishi Satomi2,3, Yoshihiro Otani4,5, Kentaro Fujii1, Joji Ishida1, Atsuhito Uneda1, Nobushige Tsuboi1, Keigo Makino1, Shuichiro Hirano1, Naoya Kemmotsu1, Ryoji Imoto1, Ryo Mizuta1, Yusuke Tomita6, Takao Yasuhara1, Kana Washio7, Hiroyuki Yanai8, Yuko Matsushita9, Yuko Hibiya9, Akihiko Yoshida2, David Capper10, Koichi Ichimura9, Isao Date1. 1. Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, kita-ku, Okayama, 700-8558, Japan. 2. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 3. Department of Pathology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan. 4. Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, kita-ku, Okayama, 700-8558, Japan. yotani@okayama-u.ac.jp. 5. Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. yotani@okayama-u.ac.jp. 6. Department of Neurosurgery and Neuroendovascular Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Moto-machi, Naka-ku, Hiroshima, 730-8518, Japan. 7. Department of Pediatrics, Okayama University Hospital, 2-5-1 Shikata-cho, kita-ku, Okayama, 700-8558, Japan. 8. Department of Pathology, Okayama University Hospital, 2-5-1 Shikata-cho, kita-ku, Okayama, 700-8558, Japan. 9. Department of Brain Disease Translational Research, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. 10. Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Abstract
PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.
PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.
Authors: Kamila M Bond; Joshua D Hughes; Amanda L Porter; Josiah Orina; Shanna Fang; Ian F Parney Journal: World Neurosurg Date: 2017-11-24 Impact factor: 2.104
Authors: David Capper; David T W Jones; Martin Sill; Volker Hovestadt; Daniel Schrimpf; Dominik Sturm; Christian Koelsche; Felix Sahm; Lukas Chavez; David E Reuss; Annekathrin Kratz; Annika K Wefers; Kristin Huang; Kristian W Pajtler; Leonille Schweizer; Damian Stichel; Adriana Olar; Nils W Engel; Kerstin Lindenberg; Patrick N Harter; Anne K Braczynski; Karl H Plate; Hildegard Dohmen; Boyan K Garvalov; Roland Coras; Annett Hölsken; Ekkehard Hewer; Melanie Bewerunge-Hudler; Matthias Schick; Roger Fischer; Rudi Beschorner; Jens Schittenhelm; Ori Staszewski; Khalida Wani; Pascale Varlet; Melanie Pages; Petra Temming; Dietmar Lohmann; Florian Selt; Hendrik Witt; Till Milde; Olaf Witt; Eleonora Aronica; Felice Giangaspero; Elisabeth Rushing; Wolfram Scheurlen; Christoph Geisenberger; Fausto J Rodriguez; Albert Becker; Matthias Preusser; Christine Haberler; Rolf Bjerkvig; Jane Cryan; Michael Farrell; Martina Deckert; Jürgen Hench; Stephan Frank; Jonathan Serrano; Kasthuri Kannan; Aristotelis Tsirigos; Wolfgang Brück; Silvia Hofer; Stefanie Brehmer; Marcel Seiz-Rosenhagen; Daniel Hänggi; Volkmar Hans; Stephanie Rozsnoki; Jordan R Hansford; Patricia Kohlhof; Bjarne W Kristensen; Matt Lechner; Beatriz Lopes; Christian Mawrin; Ralf Ketter; Andreas Kulozik; Ziad Khatib; Frank Heppner; Arend Koch; Anne Jouvet; Catherine Keohane; Helmut Mühleisen; Wolf Mueller; Ute Pohl; Marco Prinz; Axel Benner; Marc Zapatka; Nicholas G Gottardo; Pablo Hernáiz Driever; Christof M Kramm; Hermann L Müller; Stefan Rutkowski; Katja von Hoff; Michael C Frühwald; Astrid Gnekow; Gudrun Fleischhack; Stephan Tippelt; Gabriele Calaminus; Camelia-Maria Monoranu; Arie Perry; Chris Jones; Thomas S Jacques; Bernhard Radlwimmer; Marco Gessi; Torsten Pietsch; Johannes Schramm; Gabriele Schackert; Manfred Westphal; Guido Reifenberger; Pieter Wesseling; Michael Weller; Vincent Peter Collins; Ingmar Blümcke; Martin Bendszus; Jürgen Debus; Annie Huang; Nada Jabado; Paul A Northcott; Werner Paulus; Amar Gajjar; Giles W Robinson; Michael D Taylor; Zane Jaunmuktane; Marina Ryzhova; Michael Platten; Andreas Unterberg; Wolfgang Wick; Matthias A Karajannis; Michel Mittelbronn; Till Acker; Christian Hartmann; Kenneth Aldape; Ulrich Schüller; Rolf Buslei; Peter Lichter; Marcel Kool; Christel Herold-Mende; David W Ellison; Martin Hasselblatt; Matija Snuderl; Sebastian Brandner; Andrey Korshunov; Andreas von Deimling; Stefan M Pfister Journal: Nature Date: 2018-03-14 Impact factor: 49.962
Authors: Maximilian J Mair; Adelheid Wöhrer; Julia Furtner; Anika Simonovska; Barbara Kiesel; Stefan Oberndorfer; Karl Ungersböck; Christine Marosi; Felix Sahm; Johannes A Hainfellner; Karl Rössler; Matthias Preusser; Georg Widhalm; Anna S Berghoff Journal: J Neurooncol Date: 2020-04-27 Impact factor: 4.130