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TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors

ABSTRACT: Whole genome sequencing detected structural rearrangements of TERT in 17/75 high stage neuroblastoma with 5 cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted immediate up- and down-stream regions of TERT, placing in 7 cases a super-enhancer close to the breakpoints. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high stage neuroblastoma, each associated with very poor prognosis. This submission contains all newly sequenced samples only.

PROVIDER: EGAS00001001479 | EGA |

REPOSITORIES: EGA

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TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors

Project description:Whole genome sequencing detected structural rearrangements of TERT in 17/75 high stage neuroblastoma with 5 cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted immediate up- and down-stream regions of TERT, placing in 7 cases a super-enhancer close to the breakpoints. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high stage neuroblastoma, each associated with very poor prognosis

2015-10-21 | GSE73537 | GEO

ena-DATASET-AMC-07-10-2015-22:00:14:397-478 - samples

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HDAC inhibition suppresses telomerase activity in neuroblastoma cells harboring TERT rearrangements

Project description:HDAC inhibition suppresses telomerase activity in neuroblastoma cells harboring TERT rearrangements

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HDAC inhibition suppresses telomerase activity in neuroblastoma cells harboring TERT rearrangements [ChIP-Seq]

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HDAC inhibition suppresses telomerase activity in neuroblastoma cells harboring TERT rearrangements [array]

Project description:Genome wide DNA methylation profiling of high-risk TERT-rearranged neuroblastoma cells treated with solvent or HDAC inhibitor panobinostat. The Illumina HumanMethylation EPIC Beadchip was used to obtain DNA methylation profiles. Samples included 3 solvent treated samples and 3 panobinostat-treated samples after 18 h of treatment.

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Project description:Chromosomal rearrangements juxtapose the TERT coding sequence to strong enhancer elements

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Chromosomal rearrangements juxtapose the TERT coding sequence to strong enhancer elements

Project description:Chromatin immunoprecipitation (ChIP) sequencing with an anti-acetyl-H3K27 antibody showed an enhancer region rearranged to the TERT gene, and ChIP sequencing with an anti-BRD4 antibody showed BRD4 protein binding to the enhancer in TERT-rarranged neuroblasstoma PDX CCI-NB07-RMT cells

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A mechanistic classification of clinical phenotypes in neuroblastoma (TERT expression threshold cohort)

Project description:Our study proposes a precise mechanistic classification of clinical neuroblastoma phenotypes that is based on telomere maintenance mechanisms and RAS or p53 pathway mutations. A crucial factor in telomere maintenance is overexpression of TERT. We therefore determined a TERT expression threshold to identify MYCNWT TERTWT tumors whose TERT mRNA levels are comparable to those of tumors bearing MYCN or TERT alterations.

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HDAC inhibition suppresses telomerase activity in neuroblastoma cells harboring TERT rearrangements [ChIP-Seq]

Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. The three histone marks acetylation of histone 3 at lysine residue 27 (H3K27ac), trimethylation of histone 3 at lysine residue 4 (H3K4me3) and trimethylation of histone 3 at lysine residue 36 (H3K36me3) were selected, representing marks for an open chromatin structure and enable gene transcription. The two histone marks standing for a condensed chromatin state and disabled gene transcription trimethylation of histone 3 at lysine residue 27 (H3K27me3) and trimethylation of histone 3 at lysine residue 9 (H3K9me3) were chosen. ChIP sequencing of the five histone marks was investigated in high-risk TERT-rearranged neuroblastoma GI-ME-N cells treated with solvent or HDAC inhibitor panobinostat. Exemplary samples include solvent-treated and panobinostat-treated samples after 18 h of treatment.

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