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Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas

Author

Listed:
  • Sameer Agnihotri

    (University Health Network)

  • Suganth Suppiah

    (University Health Network
    University of Toronto)

  • Peter D. Tonge

    (University Health Network
    Princess Margaret Cancer Centre)

  • Shahrzad Jalali

    (University Health Network
    Princess Margaret Cancer Centre)

  • Arnavaz Danesh

    (Princess Margaret Cancer Centre)

  • Jeffery P. Bruce

    (Princess Margaret Cancer Centre)

  • Yasin Mamatjan

    (University Health Network
    Princess Margaret Cancer Centre)

  • George Klironomos

    (University Health Network)

  • Lior Gonen

    (University Health Network)

  • Karolyn Au

    (University Health Network)

  • Sheila Mansouri

    (University Health Network
    Princess Margaret Cancer Centre)

  • Sharin Karimi

    (University Health Network
    University of Toronto)

  • Felix Sahm

    (Institute of PathologyUniversity Hospital Heidelberg
    German Consortium for Translational Cancer Research (DKTK) German Cancer Research Center (DKFZ))

  • Andreas Deimling

    (Institute of PathologyUniversity Hospital Heidelberg
    German Consortium for Translational Cancer Research (DKTK) German Cancer Research Center (DKFZ))

  • Michael D. Taylor

    (University of Toronto
    Princess Margaret Cancer Centre
    The Hospital for Sick Children)

  • Normand J. Laperriere

    (University Health Network
    Princess Margaret Cancer Centre)

  • Trevor J. Pugh

    (Princess Margaret Cancer Centre
    The Hospital for Sick Children)

  • Kenneth D. Aldape

    (University Health Network
    Princess Margaret Cancer Centre
    University of Toronto)

  • Gelareh Zadeh

    (University Health Network
    University of Toronto
    Princess Margaret Cancer Centre)

Abstract

Cranial radiotherapy improves survival of the most common childhood cancers, including brain tumors and leukemia. Unfortunately, long-term survivors are faced with consequences of secondary neoplasia, including radiation-induced meningiomas (RIMs). We characterized 31 RIMs with exome/NF2 intronic sequencing, RNA sequencing and methylation profiling, and found NF2 gene rearrangements in 12/31 of RIMs, an observation previously unreported in sporadic meningioma (SM). Additionally, known recurrent mutations characteristic of SM, including AKT1, KLF4, TRAF7 and SMO, were not observed in RIMs. Combined losses of chromosomes 1p and 22q were common in RIMs (16/18 cases) and overall, chromosomal aberrations were more complex than that observed in SM. Patterns of DNA methylation profiling supported similar cell of origin between RIMs and SMs. The findings indicate that the mutational landscape of RIMs is distinct from SMs, and have significant therapeutic implications for survivors of childhood cranial radiation and the elucidation of the molecular pathogenesis of meningiomas.

Suggested Citation

  • Sameer Agnihotri & Suganth Suppiah & Peter D. Tonge & Shahrzad Jalali & Arnavaz Danesh & Jeffery P. Bruce & Yasin Mamatjan & George Klironomos & Lior Gonen & Karolyn Au & Sheila Mansouri & Sharin Kari, 2017. "Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas," Nature Communications, Nature, vol. 8(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00174-7
    DOI: 10.1038/s41467-017-00174-7
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