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@ARTICLE{Aboubakr:303121,
author = {O. Aboubakr and A. K. Wefers and V. Dangouloff-Ros and A.
Métais and P. Sievers$^*$ and L. Hasty and R. Saffroy and
G. Pierron and D. Guillemot and T. Samoyeau and N. Boddaert
and J. Grill and K. Beccaria and T. Blauwblomme and P.
Varlet and A. Tauziède-Espariat},
title = {{T}he malignant transformation of an atypical angiocentric
glioma, {MYB}-altered.},
journal = {Acta Neuropathologica Communications},
volume = {13},
number = {1},
issn = {2051-5960},
address = {London},
publisher = {Biomed Central},
reportid = {DKFZ-2025-01540},
pages = {161},
year = {2025},
abstract = {According to the current World Health Organization
classification of central nervous system tumors, the
angiocentric glioma (AG) assigned a grade 1, characterized
by recurrent MYB fusions. However, it also mentions that
increased proliferative activity and other anaplastic
features have been reported, but the clinical significance
of such findings is unclear as an increased proliferative
activity alone does not necessarily alter the benign
behavior of AGs. Most cases with 'anaplasia' were mainly
described before the molecular era. Herein, we report the
case of a 3-year-old female with epilepsy symptomatic of a
left temporo-parietal tumor. Histopathologically, the
initial tumor displayed atypical AG morphology and a
proliferation index of $1\%,$ without mitoses, or necrosis.
RNA sequencing identified a MYB::QKI fusion. After several
tumor recurrences, the last tumor sample showed strong
evidence of a histopathological transformation into a
high-grade tumor with proliferation and mitotic indexes,
necrosis and microvascular proliferation. The recurrent
tumor still harbored the same MYB::QKI fusion but acquired
an hTERT mutation. DNA-methylation analysis classified the
initial tumor as an LGG, MYB/MYBL1-altered (AG,
MYB/MYBL1-altered with a calibrated score of 0.58) while the
progression clustered with glioblastoma, IDH-wildtype, RTK1
(with a calibrated score of 0.33). The copy number variation
both at presentation and at last recurrence (CNV) exhibited
a chromosome 6 chromothripsis. The patient died from tumor
progression after an overall survival of 89 months. This
novel observation raises the question of whether this case
represents an aggressive form of MYB/MYBL1-altered LGGs
driven by an oncogenic MYB fusion, or if they are actually
high-grade gliomas that coincidentally exhibit alterations
near the MYB locus. Further reports are needed to confirm
the existence of malignant forms of LGG, MYB/MYBL1-altered,
potentially correlated with a higher grade.},
keywords = {Humans / Female / Glioma: genetics / Glioma: pathology /
Glioma: diagnostic imaging / Brain Neoplasms: genetics /
Brain Neoplasms: pathology / Brain Neoplasms: diagnostic
imaging / Child, Preschool / Proto-Oncogene Proteins c-myb:
genetics / Cell Transformation, Neoplastic: genetics / Cell
Transformation, Neoplastic: pathology / Trans-Activators:
genetics / Neoplasm Recurrence, Local: pathology / Neoplasm
Recurrence, Local: genetics / Telomerase: genetics /
Proto-Oncogene Proteins / Aggressive (Other) / Angiocentric
glioma (Other) / DNA-methylation profiling (Other) / MYB
(Other) / Proto-Oncogene Proteins c-myb (NLM Chemicals) /
MYB protein, human (NLM Chemicals) / Trans-Activators (NLM
Chemicals) / MYBL1 protein, human (NLM Chemicals) /
Telomerase (NLM Chemicals) / Proto-Oncogene Proteins (NLM
Chemicals)},
cin = {B300 / HD01},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40702569},
doi = {10.1186/s40478-025-02070-4},
url = {https://inrepo02.dkfz.de/record/303121},
}