RT Journal Article
SR Electronic
T1 Comprehensive characterization of pediatric acute myeloid leukemia reveals novel molecular features and age-specific interactions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 125609
DO 10.1101/125609
A1 Hamid Bolouri
A1 Jason E Farrar
A1 Timothy Triche, Jr
A1 Rhonda E Ries
A1 Emilia L Lim
A1 Todd A Alonzo
A1 Yussanne Ma
A1 Richard Moore
A1 Andrew Mungall
A1 Marco A Marra
A1 Jinghui Zhang
A1 Xiaotu Ma
A1 Yu Liu
A1 Yanling Liu
A1 Jaime M Guidry Auvil
A1 Tanja M Davidsen
A1 Patee Gesuwan
A1 Leandro C Hermida
A1 Bodour Salhia
A1 Stephen Capone
A1 Giridharan Ramsingh
A1 Christian Michel Zwaan
A1 Sanne Noort
A1 Stephen R Piccolo
A1 E Anders Kolb
A1 Alan S Gamis
A1 Malcolm A Smith
A1 Daniela S Gerhard
A1 Soheil Meshinchi
YR 2017
UL http://biorxiv.org/content/early/2017/06/13/125609.abstract
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.