TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors

Linda J Valentijn; Jan Koster; Danny A Zwijnenburg; Nancy E Hasselt; Peter van Sluis; Richard Volckmann; Max M van Noesel; Rani E George; Godelieve A M Tytgat; Jan J Molenaar; Rogier Versteeg

doi:10.1038/ng.3438

TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors

Linda J Valentijn, Jan Koster, Danny A Zwijnenburg, Nancy E Hasselt, Peter van Sluis, Richard Volckmann, Max M van Noesel, Rani E George, Godelieve A M Tytgat, Jan J Molenaar, Rogier Versteeg

Research output: Contribution to journal › Article › peer-review

305 Citations (Scopus)

Abstract

Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. 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.

Original language	English
Pages (from-to)	1411-4
Number of pages	4
Journal	Nature Genetics
Volume	47
Issue number	12
DOIs	https://doi.org/10.1038/ng.3438
Publication status	Published - Dec 2015

Keywords

DNA Helicases/genetics
Gene Amplification
Gene Deletion
Gene Expression Regulation, Neoplastic
Gene Rearrangement
Genome, Human
High-Throughput Nucleotide Sequencing/methods
Humans
N-Myc Proto-Oncogene Protein
Neuroblastoma/genetics
Nuclear Proteins/genetics
Oncogene Proteins/genetics
Telomerase/genetics
Telomere/genetics
X-linked Nuclear Protein

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title = "TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors",

abstract = "Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. 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. ",

keywords = "DNA Helicases/genetics, Gene Amplification, Gene Deletion, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Genome, Human, High-Throughput Nucleotide Sequencing/methods, Humans, N-Myc Proto-Oncogene Protein, Neuroblastoma/genetics, Nuclear Proteins/genetics, Oncogene Proteins/genetics, Telomerase/genetics, Telomere/genetics, X-linked Nuclear Protein",

author = "Valentijn, {Linda J} and Jan Koster and Zwijnenburg, {Danny A} and Hasselt, {Nancy E} and {van Sluis}, Peter and Richard Volckmann and {van Noesel}, {Max M} and George, {Rani E} and Tytgat, {Godelieve A M} and Molenaar, {Jan J} and Rogier Versteeg",

year = "2015",

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doi = "10.1038/ng.3438",

language = "English",

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AU - Valentijn, Linda J

AU - Koster, Jan

AU - Zwijnenburg, Danny A

AU - Hasselt, Nancy E

AU - van Sluis, Peter

AU - Volckmann, Richard

AU - van Noesel, Max M

AU - George, Rani E

AU - Tytgat, Godelieve A M

AU - Molenaar, Jan J

AU - Versteeg, Rogier

PY - 2015/12

Y1 - 2015/12

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AB - Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. 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.

KW - DNA Helicases/genetics

KW - Gene Amplification

KW - Gene Deletion

KW - Gene Expression Regulation, Neoplastic

KW - Gene Rearrangement

KW - Genome, Human

KW - High-Throughput Nucleotide Sequencing/methods

KW - Humans

KW - N-Myc Proto-Oncogene Protein

KW - Neuroblastoma/genetics

KW - Nuclear Proteins/genetics

KW - Oncogene Proteins/genetics

KW - Telomerase/genetics

KW - Telomere/genetics

KW - X-linked Nuclear Protein

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U2 - 10.1038/ng.3438

DO - 10.1038/ng.3438

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SN - 1061-4036

VL - 47

SP - 1411

EP - 1414

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors

Abstract

Keywords

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