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

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 Karimi, Felix Sahm, Andreas Deimling, Michael D. Taylor, Normand J. Laperriere, Trevor J. Pugh, Kenneth D. Aldape () and Gelareh Zadeh ()
Additional contact information
Sameer Agnihotri: University Health Network
Suganth Suppiah: University Health Network
Peter D. Tonge: University Health Network
Shahrzad Jalali: University Health Network
Arnavaz Danesh: Princess Margaret Cancer Centre
Jeffery P. Bruce: Princess Margaret Cancer Centre
Yasin Mamatjan: University Health Network
George Klironomos: University Health Network
Lior Gonen: University Health Network
Karolyn Au: University Health Network
Sheila Mansouri: University Health Network
Sharin Karimi: University Health Network
Felix Sahm: Institute of PathologyUniversity Hospital Heidelberg
Andreas Deimling: Institute of PathologyUniversity Hospital Heidelberg
Michael D. Taylor: University of Toronto
Normand J. Laperriere: University Health Network
Trevor J. Pugh: Princess Margaret Cancer Centre
Kenneth D. Aldape: University Health Network
Gelareh Zadeh: University Health Network

Nature Communications, 2017, vol. 8, issue 1, 1-7

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00174-7

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