PMID- 28960623
OWN - NLM
STAT- MEDLINE
DCOM- 20180830
LR  - 20201209
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 28
IP  - 2
DP  - 2018 Mar
TI  - Multimodal molecular analysis of astroblastoma enables reclassification of most 
      cases into more specific molecular entities.
PG  - 192-202
LID - 10.1111/bpa.12561 [doi]
AB  - Astroblastoma is a rare and controversial glioma with variable clinical behavior. 
      The diagnosis currently rests on histologic findings of a circumscribed glioma 
      with astroblastomatous pseudorosettes and vascular hyalinization. 
      Immunohistochemical studies have suggested different oncogenic drivers, such as 
      BRAF p.V600E, but very few cases have been studied using genome-wide 
      methodologies. Recent genomic profiling identified a subset of CNS embryonal 
      tumors with astroblastoma-like morphology that harbored MN1 gene fusions, termed 
      "CNS high-grade neuroepithelial tumors with MN1 alteration" (CNS-HGNET-MN1). To 
      further characterize the genetic alterations that drive astroblastomas, we 
      performed targeted next-generation sequencing (NGS) of 500 cancer-associated 
      genes in a series of eight cases. We correlated these findings with break-apart 
      fluorescence in situ hybridization (FISH) analysis of the MN1 locus and 
      genome-wide DNA methylation profiling. Four cases showed MN1 alteration by FISH, 
      including two pediatric cases that lacked other pathogenic alterations, and two 
      adult cases that harbored other cancer-associated gene mutations or copy number 
      alterations (eg, CDKN2A/B homozygous deletion, TP53, ATM and TERT promoter 
      mutations). Three of these cases grouped with the CNS-HGNET-MN1 entity by 
      methylation profiling. Two of four MN1 intact cases by FISH showed genetic 
      features of either anaplastic pleomorphic xanthoastrocytoma (BRAF p.V600E 
      mutation, CDKN2A/B homozygous deletion and TERT promoter mutation) or 
      IDH-wildtype glioblastoma (trisomy 7, monosomy 10, CDK4 amplification and TP53, 
      NRAS and TERT promoter mutations) and these cases had an aggressive clinical 
      course. Two clinically indolent cases remained unclassifiable despite multimodal 
      molecular analysis. We conclude that astroblastoma histology is not specific for 
      any entity including CNS-HGNET-MN1, and that additional genetic characterization 
      should be considered for astroblastomas, as a number of these tumors likely 
      contain a methylation profile or genetic alterations that suggest classification 
      as other tumor entities. Our heterogeneous molecular findings help to explain the 
      clinical unpredictability of astroblastoma.
CI  - (c) 2017 International Society of Neuropathology.
FAU - Wood, Matthew D
AU  - Wood MD
AUID- ORCID: 0000-0002-2385-8128
AD  - Department of Pathology, Division of Neuropathology, University of California, 
      San Francisco, CA.
FAU - Tihan, Tarik
AU  - Tihan T
AD  - Department of Pathology, Division of Neuropathology, University of California, 
      San Francisco, CA.
FAU - Perry, Arie
AU  - Perry A
AD  - Department of Pathology, Division of Neuropathology, University of California, 
      San Francisco, CA.
AD  - Department of Neurological Surgery, University of California, San Francisco, CA.
FAU - Chacko, Geeta
AU  - Chacko G
AD  - Department of Pathology, Division of Neuropathology, Christian Medical College, 
      Vellore, Tamil Nadu, India.
FAU - Turner, Clinton
AU  - Turner C
AD  - Anatomical Pathology, LabPLUS Auckland City Hospital, Auckland, New Zealand.
FAU - Pu, Cunfeng
AU  - Pu C
AD  - Department of Pathology, Allegheny General Hospital, Pittsburgh, PA.
FAU - Payne, Christopher
AU  - Payne C
AD  - Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, PA.
FAU - Yu, Alexander
AU  - Yu A
AD  - Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, PA.
FAU - Bannykh, Serguei I
AU  - Bannykh SI
AD  - Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los 
      Angeles, CA.
FAU - Solomon, David A
AU  - Solomon DA
AUID- ORCID: 0000-0003-4571-7999
AD  - Department of Pathology, Division of Neuropathology, University of California, 
      San Francisco, CA.
LA  - eng
GR  - DP5 OD021403/OD/NIH HHS/United States
GR  - T32 CA151022/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171027
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (MN1 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Brain/metabolism/*pathology/surgery
MH  - Brain Neoplasms/*classification/*genetics/metabolism/pathology
MH  - Child
MH  - Diagnosis, Differential
MH  - Female
MH  - Genotyping Techniques
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Neoplasm Grading
MH  - Neoplasms, Neuroepithelial/*classification/*genetics/metabolism/pathology
MH  - Phenotype
MH  - Retrospective Studies
MH  - Trans-Activators
MH  - Tumor Suppressor Proteins/genetics
PMC - PMC5843525
MID - NIHMS928605
OTO - NOTNLM
OT  - CNS-HGNET-MN1
OT  - DNA methylation profiling
OT  - astroblastoma
OT  - next-generation sequencing
COIS- The authors have no conflicts of interest to declare.
EDAT- 2017/09/30 06:00
MHDA- 2018/08/31 06:00
PMCR- 2017/10/27
CRDT- 2017/09/30 06:00
PHST- 2017/08/25 00:00 [received]
PHST- 2017/09/14 00:00 [accepted]
PHST- 2017/09/30 06:00 [pubmed]
PHST- 2018/08/31 06:00 [medline]
PHST- 2017/09/30 06:00 [entrez]
PHST- 2017/10/27 00:00 [pmc-release]
AID - BPA12561 [pii]
AID - 10.1111/bpa.12561 [doi]
PST - ppublish
SO  - Brain Pathol. 2018 Mar;28(2):192-202. doi: 10.1111/bpa.12561. Epub 2017 Oct 27.