{"longTitle":"TARGET high-risk neuroblastoma mutation (Pugh, Morozova 2012)","cohort":"TARGET neuroblastoma","url":"http://www.ncbi.nlm.nih.gov/pubmed/23334666","dataSubType":"somatic mutation","citation":"Nat Genet. 2013 Mar;45(3):279-84.","label":"mutation","articletitle":"The genetic landscape of high-risk neuroblastoma.","tags":["cancer","Childhood","pediatrics","sympathetic nervous system","neural crest","neuroendocrine"],"anatomical_origin":["Adrenal gland"],"name":"TARGET_neuroblastoma/NBL_mutation","dataproducer":"Pugh T, Morozova O et al","wrangling_procedure":"Download Supplementary Table 3 (All coding somatic mutations called in all cases) http://www.nature.com/ng/journal/v45/n3/extref/ng.2529-S4.xlsx, download TARGET clinical data from Supplementary Table 1 and from TARGET DCC ftp://caftpd.nci.nih.gov/pub/dcc_target/NBL/clinical/, process data into UCSC cgData repository.","sample_type":["tumor"],"assembly":"hg19","type":"mutationVector","version":"05-14-2014","primary_disease":"pediatric high-risk neuroblastoma","pmid":23334666,"description":"TARGET high-risk neuroblastoma single nucleotide mutation and small insertion and deletions.<br><br>Neuroblastoma is an embryonal malignancy of early childhood with a poor prognosis for individuals diagnosed at over 18 months of age with disseminated disease, accounting for 12% of all childhood cancer-related deaths. To determine the spectrum of somatic mutation in high-risk neuroblastoma, the authors studied 240 affected individuals using a combination of whole-exome, genome and transcriptome sequencing. This study focused on high-risk neuroblastoma with stage 4 (metastatic) disease and, preferably, those between 1.5 and 5.5 years of age at diagnosis (median, 3.4 years of age; range, 1.5-16.5 years). It reports 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.<br><br>","wholegenome":true}