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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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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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.
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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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DOI: https://doi.org/10.1038/ng.3438
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