Scientific Publications

The genetic landscape of high-risk neuroblastoma.

Publication TypeJournal Article
AuthorsPugh, TJ, Morozova O., Attiyeh EF, Asgharzadeh S., Wei JS, Auclair D., Carter SL, Cibulskis K., Hanna M., Kiezun A., Kim J., Lawrence MS, McKenna A., Pedamallu CS, Ramos AH, Shefler E., Sivachenko A., Sougnez C., Stewart C., Ally A., Birol I., Chiu R., Hirst M., Krzywinski M., Moore RA, Tam A., Thiessen N., Zhao Y., London WB, Gastier-Foster JM, Gerhard DS, Jones SJ, Lander E. S., Gabriel SB, Getz G., Marra MA, and Meyerson M.
AbstractNeuroblastoma 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.
Year of Publication2013
JournalNature genetics
Date Published (YYYY/MM/DD)2013/01/20
ISSN Number1061-4036