PMID- 27984673
OWN - NLM
STAT- MEDLINE
DCOM- 20180731
LR  - 20210904
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 28
IP  - 1
DP  - 2018 Jan
TI  - Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline 
      grade I ganglioglioma.
PG  - 103-111
LID - 10.1111/bpa.12473 [doi]
AB  - Ganglioglioma (GG) is a grade I tumor characterized by alterations in the MAPK 
      pathway, including BRAF V600E mutation. Recently, diffuse midline glioma with an 
      H3 K27M mutation was added to the WHO 2016 classification as a new grade IV 
      entity. As co-occurrence of H3 K27M and BRAF V600E mutations has been reported in 
      midline tumors and anaplastic GG, we searched for BRAF V600E and H3 K27M 
      mutations in a series of 54 paediatric midline grade I GG (midline GG) to 
      determine the frequency of double mutations and its relevance for prognosis. 
      Twenty-seven patients (50%) possessed the BRAF V600E mutation. The frequency of 
      the co-occurrence of H3F3A/BRAF mutations at diagnosis was 9.3%. No H3 K27M 
      mutation was detected in the absence of the BRAF V600E mutation. 
      Double-immunostaining revealed that BRAF V600E and H3 K27M mutant proteins were 
      present in both the glial and neuronal components. Immunopositivity for the BRAF 
      V600E mutant protein correlated with BRAF mutation status as detected by 
      massARRAY or digital droplet PCR. The median follow-up of patients with double 
      mutation was 4 years. One patient died of progressive disease 8 years after 
      diagnosis, whereas the four other patients were all alive with stable disease at 
      the last clinical follow-up (at 9 months, 1 year and 7 years) without adjuvant 
      therapy. We demonstrate in this first series of midline GGs that the H3 K27M 
      mutation can occur in association with the BRAF V600E mutation in grade I 
      glioneuronal tumors. Despite the presence of H3 K27M mutations, these cases 
      should not be graded and treated as grade IV tumors because they have a better 
      spontaneous outcome than classic diffuse midline H3 K27M-mutant glioma. These 
      data suggest that H3 K27M cannot be considered a specific hallmark of grade IV 
      diffuse gliomas and highlight the importance of integrated histomolecular 
      diagnosis in paediatric brain tumors.
CI  - (c) 2016 International Society of Neuropathology.
FAU - Pages, Melanie
AU  - Pages M
AD  - Department of Neuropathology, Sainte-Anne Hospital, Paris, France.
AD  - Paris V Descartes University, Paris, France.
AD  - Institut National de la Sante et de la Recherche Medicale, INSERM Unit 1000 
      "Neuroimaging & Psychiatry,", Universite Paris Sud, Orsay.
FAU - Beccaria, Kevin
AU  - Beccaria K
AD  - Department of Paediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, 
      France.
FAU - Boddaert, Nathalie
AU  - Boddaert N
AD  - Department of Paediatric Neuroradiology, Necker Enfants Malades Hospital, Paris, 
      France.
FAU - Saffroy, Raphael
AU  - Saffroy R
AD  - Department of Biochemistry, Paul Brousse Hospital, Paris, France.
FAU - Besnard, Aurore
AU  - Besnard A
AD  - Department of Neuropathology, Sainte-Anne Hospital, Paris, France.
FAU - Castel, David
AU  - Castel D
AD  - UMR8203 "Vectorologie et Therapeutiques Anticancereuses," CNRS, Gustave Roussy, 
      Univ. Paris-Sud, Universite Paris-Saclay, Villejuif, 94805, France.
AD  - Departement de Cancerologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. 
      Paris-Sud, Universite Paris-Saclay, Villejuif, 94805, France.
FAU - Fina, Frederic
AU  - Fina F
AD  - Service de transfert d'Oncologie Biologique, LBM APHM Marseille, France.
FAU - Barets, Doriane
AU  - Barets D
AD  - APHM, Hopital de la Timone, Service d'Anatomie Pathologique et de 
      Neuropathologie, Marseille, France.
FAU - Barret, Emilie
AU  - Barret E
AD  - UMR8203 "Vectorologie et Therapeutiques Anticancereuses," CNRS, Gustave Roussy, 
      Univ. Paris-Sud, Universite Paris-Saclay, Villejuif, 94805, France.
AD  - Departement de Cancerologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. 
      Paris-Sud, Universite Paris-Saclay, Villejuif, 94805, France.
FAU - Lacroix, Ludovic
AU  - Lacroix L
AD  - Departement de Biologie et Pathologie Medicales, Gustave Roussy, Univ. Paris-Sud, 
      Universite Paris-Saclay, Villejuif, 94805, France.
FAU - Bielle, Franck
AU  - Bielle F
AD  - Department of Neuropathology, Laboratoire Escourolle, Hopitaux Universitaires 
      Pitie Salpetriere Charles Foix, AP-HP, Paris, France.
FAU - Andreiuolo, Felipe
AU  - Andreiuolo F
AD  - Department of Neuropathology, Sainte-Anne Hospital, Paris, France.
FAU - Tauziede-Espariat, Arnault
AU  - Tauziede-Espariat A
AD  - Department of Neuropathology, Sainte-Anne Hospital, Paris, France.
FAU - Figarella-Branger, Dominique
AU  - Figarella-Branger D
AD  - APHM, Hopital de la Timone, Service d'Anatomie Pathologique et de 
      Neuropathologie, Marseille, France.
AD  - Aix-Marseille Universite, Inserm, CRO2 UMR_S 911, Marseille, France.
FAU - Puget, Stephanie
AU  - Puget S
AD  - Department of Paediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, 
      France.
FAU - Grill, Jacques
AU  - Grill J
AD  - UMR8203 "Vectorologie et Therapeutiques Anticancereuses," CNRS, Gustave Roussy, 
      Univ. Paris-Sud, Universite Paris-Saclay, Villejuif, 94805, France.
AD  - Departement de Cancerologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. 
      Paris-Sud, Universite Paris-Saclay, Villejuif, 94805, France.
FAU - Chretien, Fabrice
AU  - Chretien F
AD  - Department of Neuropathology, Sainte-Anne Hospital, Paris, France.
AD  - Paris V Descartes University, Paris, France.
AD  - Infection & Epidemiology Department, Human Histopathology and Animal Models Unit, 
      Institut Pasteur, Paris, France.
FAU - Varlet, Pascale
AU  - Varlet P
AD  - Department of Neuropathology, Sainte-Anne Hospital, Paris, France.
AD  - Paris V Descartes University, Paris, France.
AD  - Institut National de la Sante et de la Recherche Medicale, INSERM Unit 1000 
      "Neuroimaging & Psychiatry,", Universite Paris Sud, Orsay.
LA  - eng
PT  - Journal Article
DEP - 20170208
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (Histones)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - Adolescent
MH  - Brain Neoplasms/diagnostic imaging/*genetics/pathology/therapy
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Follow-Up Studies
MH  - Ganglioglioma/diagnostic imaging/*genetics/pathology/therapy
MH  - Histones/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - *Mutation
MH  - Neoplasm Grading
MH  - Proto-Oncogene Proteins B-raf/*genetics
MH  - Spinal Cord Neoplasms/diagnostic imaging/*genetics/pathology/therapy
MH  - Treatment Outcome
PMC - PMC8028391
OTO - NOTNLM
OT  - BRAF V600E
OT  - H3 K27M
OT  - ganglioglioma
OT  - midline
COIS- The authors declare that they have no conflict of interest except Pascale Varlet 
      (Hoffmann La roche, Novartis and Boehringer-Ingelheim) and Jacques Grill 
      (Novartis, Roche, Bristol-Myers Squibb).
EDAT- 2016/12/17 06:00
MHDA- 2018/08/01 06:00
PMCR- 2017/02/08
CRDT- 2016/12/17 06:00
PHST- 2016/10/18 00:00 [received]
PHST- 2016/12/01 00:00 [accepted]
PHST- 2016/12/17 06:00 [pubmed]
PHST- 2018/08/01 06:00 [medline]
PHST- 2016/12/17 06:00 [entrez]
PHST- 2017/02/08 00:00 [pmc-release]
AID - BPA12473 [pii]
AID - 10.1111/bpa.12473 [doi]
PST - ppublish
SO  - Brain Pathol. 2018 Jan;28(1):103-111. doi: 10.1111/bpa.12473. Epub 2017 Feb 8.