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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

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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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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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