PMID- 28879901
OWN - NLM
STAT- MEDLINE
DCOM- 20190716
LR  - 20211204
IS  - 0028-3886 (Print)
IS  - 0028-3886 (Linking)
VI  - 65
IP  - 5
DP  - 2017 Sep-Oct
TI  - BRAF gene alterations and enhanced mammalian target of rapamycin signaling in 
      gangliogliomas.
PG  - 1076-1082
LID - 10.4103/neuroindia.NI_207_17 [doi]
AB  - BACKGROUND: Gangliogliomas (GGs) are slow-growing glioneuronal tumors seen in 
      children and young adults. They are associated with intractable epilepsy, and 
      have recently been found to harbor BRAF (B- rapidly accelerated fibrosarcoma) 
      gene mutations. However, the mammalian target of rapamycin (mTOR) signaling 
      pathway, downstream of BRAF, has not been evaluated extensively in GGs. MATERIALS 
      AND METHODS: GG cases were retrieved, clinical data obtained, and 
      histopathological features reviewed. Sequencing for BRAF V600E mutation, analysis 
      of BRAF copy number by quantitative real-time polymerase chain reaction, and 
      immunohistochemistry for mTOR pathway markers p-S6 and p-4EBP1 were performed. 
      RESULTS: Sixty-four cases of GG were identified (0.9% of central nervous system 
      tumors). Of these, 28 had sufficient tumor tissue for further evaluation. Mixed 
      glial and neuronal morphology was the commonest (64%) type. Focal cortical 
      dysplasia was identified in the adjacent cortex (6 cases). BRAF V600E mutation 
      was identified in 30% of GGs; BRAF copy number gain was observed in 50% of them. 
      p-S6 and p-4EBP1 immunopositivity was seen in 57% cases each. Thus, mTOR pathway 
      activation was seen in 81% cases, and was independent of BRAF alterations. 87% 
      patients had Engel grade I outcome, while 13% had Engel grade II outcome. Both 
      the Engel grade II cases analyzed showed BRAF V600E mutation. CONCLUSION: BRAF 
      V600E mutation is frequent in GGs, as is BRAF gain; the former may serve as a 
      target for personalized therapy in patients with residual tumors, necessitating 
      its assessment in routine pathology reporting of these tumors. Evidence of mTOR 
      pathway activation highlights similarities in the pathogenetic mechanisms 
      underlying GG and focal cortical dysplasia, and suggests that mTOR inhibitors may 
      be of utility in GG patients with persistent seizures after surgery.
FAU - Kakkar, Aanchal
AU  - Kakkar A
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Majumdar, Atreye
AU  - Majumdar A
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Pathak, Pankaj
AU  - Pathak P
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Kumar, Anupam
AU  - Kumar A
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Kumari, Kalpana
AU  - Kumari K
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Tripathi, Manjari
AU  - Tripathi M
AD  - Department of Neurology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Sharma, Mehar C
AU  - Sharma MC
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Suri, Vaishali
AU  - Suri V
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Tandon, Vivek
AU  - Tandon V
AD  - Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Chandra, Sarat P
AU  - Chandra SP
AD  - Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Sarkar, Chitra
AU  - Sarkar C
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
LA  - eng
PT  - Journal Article
PL  - India
TA  - Neurol India
JT  - Neurology India
JID - 0042005
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Brain Neoplasms/*genetics/*metabolism
MH  - Child
MH  - Female
MH  - Ganglioglioma/*genetics/*metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Proto-Oncogene Proteins B-raf/*genetics
MH  - Retrospective Studies
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Young Adult
EDAT- 2017/09/08 06:00
MHDA- 2019/07/17 06:00
CRDT- 2017/09/08 06:00
PHST- 2017/09/08 06:00 [entrez]
PHST- 2017/09/08 06:00 [pubmed]
PHST- 2019/07/17 06:00 [medline]
AID - ni_2017_65_5_1076_214042 [pii]
AID - 10.4103/neuroindia.NI_207_17 [doi]
PST - ppublish
SO  - Neurol India. 2017 Sep-Oct;65(5):1076-1082. doi: 10.4103/neuroindia.NI_207_17.