David Meyronet1, Maud Esteban-Mader1, Charlotte Bonnet1, Marie-Odile Joly1, Emmanuelle Uro-Coste1, Alexandra Amiel-Benouaich1, Fabien Forest1, Cécilia Rousselot-Denis1, Fanny Burel-Vandenbos1, Véronique Bourg1, Jacques Guyotat1, Tanguy Fenouil1, Anne Jouvet1, Jérôme Honnorat1, François Ducray1. 1. Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neuropathologie, Lyon, Cedex, France; Université Claude Bernard Lyon 1, Lyon, France; Department of Cancer Cell Plasticity, Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, Lyon, France; Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neuro-Oncologie, Lyon, Cedex, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Anatomie et Cytologie Pathologiques, Lyon, Cedex, France; CHU Toulouse, Hôpital de Rangueil, Service d'Anatomie et Cytologie Pathologique, Toulouse, France; CHU Toulouse, Hôpital Pierre-Paul Riquet, Service de Neurologie, Toulouse, France; CHU Saint-Etienne, Hôpital Nord, Service d'Anatomie et Cytologie Pathologique, Saint-Etienne, France; CHU de Tours, Hôpital Bretonneau, Service d'anatomie et cytologie pathologiques, Tours, Cedex, France; CHU de Nice, Hôpital Pasteur, Service d'anatomie et cytologie pathologiques, Nice, France; CHU de Nice, Hôpital Pasteur, Service de neurologie, Nice, France; Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neurochirurgie D, Lyon, Cedex, France; Institut NeuroMyoGene, INSERM 1217/CNRS 5310, Université de Lyon, Lyon, France.
Abstract
BACKGROUND: Diffuse H3 K27M-mutant gliomas occur primarily in children but can also be encountered in adults. The aim of this study was to describe the characteristics of H3 K27M-mutant gliomas in adults. METHODS: We analyzed the characteristics of 21 adult H3 K27M-mutant gliomas and compared them with those of 135 adult diffuse gliomas without histone H3 and without isocitrate dehydrogenase (IDH) mutation (IDH/H3 wild type). RESULTS: The median age at diagnosis in H3 K27M-mutant gliomas was 32 years (range: 18-82 y). All tumors had a midline location (spinal cord n = 6, thalamus n = 5, brainstem n = 5, cerebellum n = 3, hypothalamus n = 1, and pineal region n = 1) and were IDH and BRAF-V600E wild type. The identification of an H3 K27M mutation significantly impacted the diagnosis in 3 patients (14%) for whom the histological aspect initially suggested a diffuse low-grade glioma and in 7 patients (33%) for whom pathological analysis hesitated between a diffuse glioma, ganglioglioma, or pilocytic astrocytoma. Compared with IDH/H3 wild-type gliomas, H3 K27M-mutant gliomas were diagnosed at an earlier age (32 vs 64 y, P < .001), always had a midline location (21/21 vs 21/130, P < .001), less frequently had a methylated MGMT promoter (1/21 vs 52/129, P = .002), and lacked EGFR amplification (0/21 vs 26/128, P = .02). The median survival was 19.6 months in H3 K27M-mutant gliomas and 17 months in IDH/H3 wild-type gliomas (P = .3). CONCLUSION: In adults, as in children, H3 K27M mutations define a distinct subgroup of IDH wild-type gliomas characterized by a constant midline location, low rate of MGMT promoter methylation, and poor prognosis.
BACKGROUND: Diffuse H3 K27M-mutant gliomas occur primarily in children but can also be encountered in adults. The aim of this study was to describe the characteristics of H3 K27M-mutant gliomas in adults. METHODS: We analyzed the characteristics of 21 adult H3 K27M-mutant gliomas and compared them with those of 135 adult diffuse gliomas without histone H3 and without isocitrate dehydrogenase (IDH) mutation (IDH/H3 wild type). RESULTS: The median age at diagnosis in H3 K27M-mutant gliomas was 32 years (range: 18-82 y). All tumors had a midline location (spinal cord n = 6, thalamus n = 5, brainstem n = 5, cerebellum n = 3, hypothalamus n = 1, and pineal region n = 1) and were IDH and BRAF-V600E wild type. The identification of an H3 K27M mutation significantly impacted the diagnosis in 3 patients (14%) for whom the histological aspect initially suggested a diffuse low-grade glioma and in 7 patients (33%) for whom pathological analysis hesitated between a diffuse glioma, ganglioglioma, or pilocytic astrocytoma. Compared with IDH/H3 wild-type gliomas, H3 K27M-mutant gliomas were diagnosed at an earlier age (32 vs 64 y, P < .001), always had a midline location (21/21 vs 21/130, P < .001), less frequently had a methylated MGMT promoter (1/21 vs 52/129, P = .002), and lacked EGFR amplification (0/21 vs 26/128, P = .02). The median survival was 19.6 months in H3 K27M-mutant gliomas and 17 months in IDH/H3 wild-type gliomas (P = .3). CONCLUSION: In adults, as in children, H3 K27M mutations define a distinct subgroup of IDH wild-type gliomas characterized by a constant midline location, low rate of MGMT promoter methylation, and poor prognosis.
Authors: David A Solomon; Matthew D Wood; Tarik Tihan; Andrew W Bollen; Nalin Gupta; Joanna J J Phillips; Arie Perry Journal: Brain Pathol Date: 2015-12-14 Impact factor: 6.508
Authors: David N Louis; Arie Perry; Guido Reifenberger; Andreas von Deimling; Dominique Figarella-Branger; Webster K Cavenee; Hiroko Ohgaki; Otmar D Wiestler; Paul Kleihues; David W Ellison Journal: Acta Neuropathol Date: 2016-05-09 Impact factor: 17.088
Authors: Dominik Sturm; Hendrik Witt; Volker Hovestadt; Dong-Anh Khuong-Quang; David T W Jones; Carolin Konermann; Elke Pfaff; Martje Tönjes; Martin Sill; Sebastian Bender; Marcel Kool; Marc Zapatka; Natalia Becker; Manuela Zucknick; Thomas Hielscher; Xiao-Yang Liu; Adam M Fontebasso; Marina Ryzhova; Steffen Albrecht; Karine Jacob; Marietta Wolter; Martin Ebinger; Martin U Schuhmann; Timothy van Meter; Michael C Frühwald; Holger Hauch; Arnulf Pekrun; Bernhard Radlwimmer; Tim Niehues; Gregor von Komorowski; Matthias Dürken; Andreas E Kulozik; Jenny Madden; Andrew Donson; Nicholas K Foreman; Rachid Drissi; Maryam Fouladi; Wolfram Scheurlen; Andreas von Deimling; Camelia Monoranu; Wolfgang Roggendorf; Christel Herold-Mende; Andreas Unterberg; Christof M Kramm; Jörg Felsberg; Christian Hartmann; Benedikt Wiestler; Wolfgang Wick; Till Milde; Olaf Witt; Anders M Lindroth; Jeremy Schwartzentruber; Damien Faury; Adam Fleming; Magdalena Zakrzewska; Pawel P Liberski; Krzysztof Zakrzewski; Peter Hauser; Miklos Garami; Almos Klekner; Laszlo Bognar; Sorana Morrissy; Florence Cavalli; Michael D Taylor; Peter van Sluis; Jan Koster; Rogier Versteeg; Richard Volckmann; Tom Mikkelsen; Kenneth Aldape; Guido Reifenberger; V Peter Collins; Jacek Majewski; Andrey Korshunov; Peter Lichter; Christoph Plass; Nada Jabado; Stefan M Pfister Journal: Cancer Cell Date: 2012-10-16 Impact factor: 31.743
Authors: T Walter; B van Brakel; C Vercherat; V Hervieu; J Forestier; J-A Chayvialle; Y Molin; C Lombard-Bohas; M-O Joly; J-Y Scoazec Journal: Br J Cancer Date: 2015-01-13 Impact factor: 7.640
Authors: M Labussière; A L Di Stefano; V Gleize; B Boisselier; M Giry; S Mangesius; A Bruno; R Paterra; Y Marie; A Rahimian; G Finocchiaro; R S Houlston; K Hoang-Xuan; A Idbaih; J-Y Delattre; K Mokhtari; M Sanson Journal: Br J Cancer Date: 2014-10-14 Impact factor: 7.640
Authors: Rupesh Kotecha; Minesh P Mehta; Eric L Chang; Paul D Brown; John H Suh; Simon S Lo; Sunit Das; Haider H Samawi; Julia Keith; James Perry; Arjun Sahgal Journal: Neuro Oncol Date: 2019-06-10 Impact factor: 12.300
Authors: Michael Zhang; Richard Li; Erqi L Pollom; Arya Amini; Savita Dandapani; Gordon Li Journal: J Clin Neurosci Date: 2020-11-06 Impact factor: 1.961