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@ARTICLE{Bongaarts:177241,
author = {A. Bongaarts and C. Mijnsbergen and J. J. Anink and F. E.
Jansen and W. G. M. Spliet and W. F. A. den Dunnen and R.
Coras and I. Blümcke and W. Paulus and V. E. Gruber and T.
Scholl and J. A. Hainfellner and M. Feucht and K. Kotulska
and S. Jozwiak and W. Grajkowska and A. M. Buccoliero and C.
Caporalini and F. Giordano and L. Genitori and F.
Söylemezoğlu and J. Pimentel and D. T. W. Jones$^*$ and B.
P. Scicluna and A. Y. N. Schouten-van Meeteren and A.
Mühlebner and J. D. Mills and E. Aronica},
title = {{D}istinct {DNA} {M}ethylation {P}atterns of {S}ubependymal
{G}iant {C}ell {A}strocytomas in {T}uberous {S}clerosis
{C}omplex.},
journal = {Cellular and molecular neurobiology},
volume = {42},
number = {8},
issn = {1573-6830},
address = {Dordrecht},
publisher = {Springer Science + Business Media B.V},
reportid = {DKFZ-2021-02375},
pages = {2863-2892},
year = {2022},
note = {2022 Nov;42(8):2863-2892},
abstract = {Tuberous sclerosis complex (TSC) is a monogenic disorder
caused by mutations in either the TSC1 or TSC2 gene, two key
regulators of the mechanistic target of the rapamycin
complex pathway. Phenotypically, this leads to growth and
formation of hamartomas in several organs, including the
brain. Subependymal giant cell astrocytomas (SEGAs) are
low-grade brain tumors commonly associated with TSC.
Recently, gene expression studies provided evidence that the
immune system, the MAPK pathway and extracellular matrix
organization play an important role in SEGA development.
However, the precise mechanisms behind the gene expression
changes in SEGA are still largely unknown, providing a
potential role for DNA methylation. We investigated the
methylation profile of SEGAs using the Illumina Infinium
HumanMethylation450 BeadChip (SEGAs n = 42, periventricular
control n = 8). The SEGA methylation profile was enriched
for the adaptive immune system, T cell activation, leukocyte
mediated immunity, extracellular structure organization and
the ERK1 $\&$ ERK2 cascade. More interestingly, we
identified two subgroups in the SEGA methylation data and
show that the differentially expressed genes between the two
subgroups are related to the MAPK cascade and adaptive
immune response. Overall, this study shows that the immune
system, the MAPK pathway and extracellular matrix
organization are also affected on DNA methylation level,
suggesting that therapeutic intervention on DNA level could
be useful for these specific pathways in SEGA. Moreover, we
identified two subgroups in SEGA that seem to be driven by
changes in the adaptive immune response and MAPK pathway and
could potentially hold predictive information on target
treatment response.},
keywords = {Low-grade glioma (Other) / Methylation (Other) /
RNA-sequencing (Other) / SEGA (Other) / TSC (Other)},
cin = {B360},
ddc = {610},
cid = {I:(DE-He78)B360-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34709498},
doi = {10.1007/s10571-021-01157-5},
url = {https://inrepo02.dkfz.de/record/177241},
}