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000177241 0247_ $$2doi$$a10.1007/s10571-021-01157-5
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000177241 0247_ $$2ISSN$$a0272-4340
000177241 0247_ $$2ISSN$$a1573-6830
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000177241 041__ $$aEnglish
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000177241 1001_ $$00000-0003-1451-4240$$aBongaarts, Anika$$b0
000177241 245__ $$aDistinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex.
000177241 260__ $$aDordrecht$$bSpringer Science + Business Media B.V$$c2022
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000177241 500__ $$a2022 Nov;42(8):2863-2892
000177241 520__ $$aTuberous 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.
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000177241 650_7 $$2Other$$aLow-grade glioma
000177241 650_7 $$2Other$$aMethylation
000177241 650_7 $$2Other$$aRNA-sequencing
000177241 650_7 $$2Other$$aSEGA
000177241 650_7 $$2Other$$aTSC
000177241 7001_ $$aMijnsbergen, Caroline$$b1
000177241 7001_ $$aAnink, Jasper J$$b2
000177241 7001_ $$aJansen, Floor E$$b3
000177241 7001_ $$aSpliet, Wim G M$$b4
000177241 7001_ $$aden Dunnen, Wilfred F A$$b5
000177241 7001_ $$aCoras, Roland$$b6
000177241 7001_ $$aBlümcke, Ingmar$$b7
000177241 7001_ $$aPaulus, Werner$$b8
000177241 7001_ $$aGruber, Victoria E$$b9
000177241 7001_ $$aScholl, Theresa$$b10
000177241 7001_ $$aHainfellner, Johannes A$$b11
000177241 7001_ $$aFeucht, Martha$$b12
000177241 7001_ $$aKotulska, Katarzyna$$b13
000177241 7001_ $$aJozwiak, Sergiusz$$b14
000177241 7001_ $$aGrajkowska, Wieslawa$$b15
000177241 7001_ $$aBuccoliero, Anna Maria$$b16
000177241 7001_ $$aCaporalini, Chiara$$b17
000177241 7001_ $$aGiordano, Flavio$$b18
000177241 7001_ $$aGenitori, Lorenzo$$b19
000177241 7001_ $$aSöylemezoğlu, Figen$$b20
000177241 7001_ $$aPimentel, José$$b21
000177241 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b22$$udkfz
000177241 7001_ $$aScicluna, Brendon P$$b23
000177241 7001_ $$aSchouten-van Meeteren, Antoinette Y N$$b24
000177241 7001_ $$aMühlebner, Angelika$$b25
000177241 7001_ $$aMills, James D$$b26
000177241 7001_ $$aAronica, Eleonora$$b27
000177241 773__ $$0PERI:(DE-600)1496697-9$$a10.1007/s10571-021-01157-5$$n8$$p2863-2892$$tCellular and molecular neurobiology$$v42$$x1573-6830$$y2022
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