The genetic landscape of high-risk neuroblastoma
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Lander_The genetic landscape.pdf
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685.54 KB
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Author(s)
Lander, Eric Steven
Date Issued
January 2013
Journal
Nature Genetics
Publisher
Nature Publishing Group
Citation
Pugh, Trevor J, Olena Morozova, Edward F Attiyeh, Shahab Asgharzadeh, Jun S Wei, Daniel Auclair, Scott L Carter, et al. “The genetic landscape of high-risk neuroblastoma.” Nature Genetics 45, no. 3 (January 20, 2013): 279-284.
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Author's final manuscript
Abstract
Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1038/ng.2529
