%0 Journal Article %A Hamid Bolouri %A Jason E Farrar %A Timothy Triche, Jr %A Rhonda E Ries %A Emilia L Lim %A Todd A Alonzo %A Yussanne Ma %A Richard Moore %A Andrew Mungall %A Marco A Marra %A Jinghui Zhang %A Xiaotu Ma %A Yu Liu %A Yanling Liu %A Jaime M Guidry Auvil %A Tanja M Davidsen %A Patee Gesuwan %A Leandro C Hermida %A Bodour Salhia %A Stephen Capone %A Giridharan Ramsingh %A Christian Michel Zwaan %A Sanne Noort %A Stephen R Piccolo %A E Anders Kolb %A Alan S Gamis %A Malcolm A Smith %A Daniela S Gerhard %A Soheil Meshinchi %T Comprehensive characterization of pediatric acute myeloid leukemia reveals novel molecular features and age-specific interactions %D 2017 %R 10.1101/125609 %J bioRxiv %P 125609 %X We present the molecular landscape of pediatric acute myeloid leukemia (AML), characterizing nearly 1,000 participants in Children’s Oncology Group (COG) AML trials. The COG/NCI TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA, and miRNA sequencing, and CpG methylation profiling. Validated DNA variants revealed diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. We find that somatic structural variants, including novel gene fusions, and focal MBNL1, ZEB2, and ELF1 deletions are common in younger patients, whereas short sequence variants predominate in adults. Mutations of DNMT3A and TP53, common in adults, are conspicuously absent from virtually all pediatric patients. Pediatric AML harbors novel GATA2, FLT3, and CBL mutations, recurrent MYC-ITD, frequent NRAS, KRAS, and WT1 mutations, and recurrent promoter hypermethylation of activating NK cell ligands. Across all age groups, we find distinct molecular alterations with clinical implications, suggesting a need for age-specific targeted therapies. %U https://www.biorxiv.org/content/biorxiv/early/2017/06/13/125609.full.pdf