Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas
| Autor: | Andreas von Deimling, Michael D. Taylor, Trevor J. Pugh, Peter D. Tonge, Suganth Suppiah, George Klironomos, Karolyn Au, Sameer Agnihotri, Sheila Mansouri, Felix Sahm, Lior Gonen, Arnavaz Danesh, Kenneth Aldape, Shahrzad Jalali, Yasin Mamatjan, Normand Laperriere, Sharin Karimi, Jeff Bruce, Gelareh Zadeh |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Neoplasms Radiation-Induced Cell of origin General Physics and Astronomy AKT1 Bioinformatics Therapeutic radiation 0302 clinical medicine Cancer Survivors Meningeal Neoplasms Exome Gene Rearrangement Multidisciplinary Leukemia Methylation Middle Aged 3. Good health KLF4 030220 oncology & carcinogenesis Female Meningioma Adult Science Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Kruppel-Like Factor 4 Young Adult Genes Neurofibromatosis 2 medicine otorhinolaryngologic diseases Humans Cerebellar Neoplasms neoplasms Aged Sequence Analysis RNA General Chemistry Sequence Analysis DNA DNA Methylation medicine.disease nervous system diseases Case-Control Studies Mutation Cancer research sense organs Cranial Irradiation 030217 neurology & neurosurgery Medulloblastoma |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-7 (2017) |
| ISSN: | 2041-1723 |
| Popis: | 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. Radiation-induced meningiomas are often more aggressive than sporadic ones. In this study, the authors perform an exome, methylation and RNA-seq analysis of 31 cases of radiation-induced meningioma and show NF2 rearrangement, an observation previously unreported in the sporadic tumors. |
| Databáze: | OpenAIRE |
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