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TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors

Nature Genetics volume 47, pages 1411–1414 (2015)Cite this article

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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.

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Figure 1: TERT rearrangements activate TERT mRNA expression in neuroblastoma tumors.
Figure 2: Chromosomal aberrations and mutations in high-stage neuroblastoma and the prognostic value of these genetic changes.

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Gene Expression Omnibus

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Gene Expression Omnibus

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Acknowledgements

This study was supported by grants from the Villa Joep Foundation, the Children Cancer-Free Foundation (KIKA) and the KWF/Netherlands Cancer Foundation and by a European Union European Research Council (ERC) Advanced grant to R. Versteeg.

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Author notes

  1. Linda J Valentijn and Jan Koster: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands

    Linda J Valentijn, Jan Koster, Danny A Zwijnenburg, Nancy E Hasselt, Peter van Sluis, Richard Volckmann, Jan J Molenaar & Rogier Versteeg

  2. Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

    Max M van Noesel & Godelieve A M Tytgat

  3. Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, Massachusetts, USA

    Rani E George

  4. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA

    Rani E George

  5. Department of Pediatric Oncology, Academic Medical Center, Amsterdam, the Netherlands

    Godelieve A M Tytgat

Authors
  1. Linda J Valentijn
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  2. Jan Koster
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  3. Danny A Zwijnenburg
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  4. Nancy E Hasselt
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  5. Peter van Sluis
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  6. Richard Volckmann
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  7. Max M van Noesel
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  8. Rani E George
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  9. Godelieve A M Tytgat
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  10. Jan J Molenaar
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  11. Rogier Versteeg
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Contributions

L.J.V., J.K., J.J.M. and R. Versteeg designed the study and prepared the manuscript. L.J.V., N.E.H. and P.v.S. performed experiments. J.K., D.A.Z., R. Volckmann and L.J.V. analyzed data. G.A.M.T. and M.M.v.N. contributed patient material. R.E.G. provided enhancer data.

Corresponding author

Correspondence to Rogier Versteeg.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8. (PDF 6950 kb)

Supplementary Table 1

Clinical information on the patients. (XLSX 20 kb)

Supplementary Table 2

Breakpoint analysis of TERT rearrangements. (XLSX 13 kb)

Supplementary Table 3

Enhancer enrichment simulation on 12 random locations. (XLSX 12 kb)

Supplementary Table 4

Cox proportional hazard analysis for MYCN, TERT and ATRX events. (XLSX 11 kb)

Supplementary Table 5

Primers used for RT-PCR. (XLSX 11 kb)

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Valentijn, L., Koster, J., Zwijnenburg, D. et al. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet 47, 1411–1414 (2015). https://doi.org/10.1038/ng.3438

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