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Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis
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Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis
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Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis
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Journal Article
Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis
2019
Overview
Astroblastoma (AB) is a rare CNS tumor demonstrating abundant
astroblastomatous pseudorosettes.
Its molecular features have not been comprehensively studied and its status as a tumor entity is controversial. We analyzed a cohort of 27 histologically-defined ABs using DNA methylation profiling, copy number analysis, FISH and site-directed sequencing. Most cases demonstrated mutually exclusive
MN1
rearrangements (
n
= 10) or
BRAF
V600E
mutations (
n
= 7). Two additional cases harbored
RELA
rearrangements. Other cases lacked these specific genetic alterations (
n
= 8). By DNA methylation profiling, tumors with
MN1
or
RELA
rearrangement clustered with high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) and
RELA
-fusion ependymoma, respectively. In contrast,
BRAF
V600E
-mutant tumors grouped with pleomorphic xanthoastrocytoma (PXA). Six additional tumors clustered with either supratentorial pilocytic astrocytoma and ganglioglioma (LGG-PA/GG-ST), normal or reactive cerebrum, or with no defined DNA methylation class. While certain histologic features favored one genetic group over another, no group could be reliably distinguished by histopathology alone. Survival analysis between genetic AB subtypes was limited by sample size, but showed that
MN1
-rearranged AB tumors were characterized by better overall survival compared to other genetic subtypes, in fact, significantly better than
BRAF
V600E
-mutant tumors (
P
= 0.013). Our data confirm that histologically-defined ABs are molecularly heterogeneous and do not represent a single entity. They rather encompass several low- to higher-grade glial tumors including neuroepithelial tumors with MN1 rearrangement, PXA-like tumors, RELA ependymomas, and possibly yet uncharacterized lesions. Genetic subtyping of tumors exhibiting AB histology, particularly determination of
MN1
and
BRAF
V600E
status, is necessary for important prognostic and possible treatment implications.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
/ Adult
/ Aged
/ Analysis
/ Biomedical and Life Sciences
/ Brain
/ Child
/ DNA
/ Female
/ Gene Rearrangement - genetics
/ Humans
/ Male
/ Neoplasms, Neuroepithelial - genetics
/ Neoplasms, Neuroepithelial - mortality
/ Neoplasms, Neuroepithelial - pathology
/ Proto-Oncogene Proteins B-raf - genetics
/ Tumor Suppressor Proteins - genetics
/ Tumors
