Journal Article

DKFZ-2020-00660

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Pilocytic Astrocytoma demethylation and transcriptional landscapes link bZIP transcription factors to immune response.

Aichmüller, C. (First author)DKFZ* ; Iskar, M.DKFZ* ; Jones, D. T. W.DKFZ* ; Korshunov, A.DKFZ* ; Radlwimmer, B.DKFZ* ; Kool, M.DKFZ* ; Ernst, A.DKFZ* ; Pfister, S. M.DKFZ* ; Lichter, P.DKFZ* ; Zapatka, M. (Last author)DKFZ*

2020
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noaa035

Abstract: Pilocytic Astrocytoma (PA) is the most common pediatric brain tumor. While genome and transcriptome landscapes are well-studied, data of the complete methylome, tumor cell composition and immune infiltration are scarce.We generated whole genome bisulfite sequence data (WGBS) of nine PAs and 16 control samples and integrated available 154 PA and 57 control methylation array data. RNA sequence data of 49 PAs and 11 control samples as well as gene expression arrays of 248 PAs and 28 controls were used to assess transcriptional activity.DNA-methylation patterns of partially-methylated domains (PMDs) suggested high stability of the methylomes during tumorigenesis. Comparing tumor and control tissues of infra- and supratentorial location using methylation arrays revealed site specific pattern. Analysis of WGBS data revealed 9381 significantly differentially methylated regions (DMRs) in PA vs. control tissue. Enhancers and transcription factor (TF) motifs of five distinct TF families were found to be enriched in DMRs. Methylation together with gene expression data based in-silico tissue deconvolution analysis indicated a striking variation in the immune cell infiltration in PA. A TF network analysis showed a regulatory relation between bZIP transcription factors and genes involved in immune related processes.We provide evidence for a link of focal methylation differences and differential gene expression to immune infiltration.

Note: #EA:B060#LA:B060#2020 Sep 29;22(9):1327-1338

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Contributing Institute(s):

1. B060 Molekulare Genetik (B060)
2. Pediatric Glioma (B360)
3. DKTK HD zentral (HD01)
4. B062 Pädiatrische Neuroonkologie (B062)
5. KKE Neuropathologie (B300)
6. Genominstabilität in Tumoren (B420)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2020

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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