PT  - JOURNAL ARTICLE
AU  - Hamid Bolouri
AU  - Jason E Farrar
AU  - Timothy Triche, Jr
AU  - Rhonda E Ries
AU  - Emilia L Lim
AU  - Todd A Alonzo
AU  - Yussanne Ma
AU  - Richard Moore
AU  - Andrew Mungall
AU  - Marco A Marra
AU  - Jinghui Zhang
AU  - Xiaotu Ma
AU  - Yu Liu
AU  - Yanling Liu
AU  - Jaime M Guidry Auvil
AU  - Tanja M Davidsen
AU  - Patee Gesuwan
AU  - Leandro C Hermida
AU  - Bodour Salhia
AU  - Stephen Capone
AU  - Giridharan Ramsingh
AU  - Christian Michel Zwaan
AU  - Sanne Noort
AU  - Stephen R Piccolo
AU  - E Anders Kolb
AU  - Alan S Gamis
AU  - Malcolm A Smith
AU  - Daniela S Gerhard
AU  - Soheil Meshinchi
TI  - Comprehensive characterization of pediatric acute myeloid leukemia reveals novel molecular features and age-specific interactions
AID  - 10.1101/125609
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 125609
4099  - http://biorxiv.org/content/early/2017/06/13/125609.short
4100  - http://biorxiv.org/content/early/2017/06/13/125609.full
AB  - 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.