The genomic landscape of core-binding factor acute myeloid leukemias

Item Type:	Article
Title:	The genomic landscape of core-binding factor acute myeloid leukemias
Creators Name:	Faber, Z.J. and Chen, X. and Gedman, A.L. and Boggs, K. and Cheng, J. and Ma, J. and Radtke, I. and Chao, J.R. and Walsh, M.P. and Song, G. and Andersson, A.K. and Dang, J. and Dong, L. and Liu, Y. and Huether, R. and Cai, Z. and Mulder, H. and Wu, G. and Edmonson, M. and Rusch, M. and Qu, C. and Li, Y. and Vadodaria, B. and Wang, J. and Hedlund, E. and Cao, X. and Yergeau, D. and Nakitandwe, J. and Pounds, S.B. and Shurtleff, S. and Fulton, R.S. and Fulton, L.L. and Easton, J. and Parganas, E. and Pui, C.H. and Rubnitz, J.E. and Ding, L. and Mardis, E.R. and Wilson, R.K. and Gruber, T.A. and Mullighan, C.G. and Schlenk, R.F. and Paschka, P. and Döhner, K. and Döhner, H. and Bullinger, L. and Zhang, J. and Klco, J.M. and Downing, J.R.
Abstract:	Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
Keywords:	Acute Myeloid Leukemia, Core Binding Factors, Fusion Oncogene Proteins, Genomics, Mutation, Tumor Biomarkers
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	48
Number:	12
Page Range:	1551-1556
Date:	December 2016
Additional Information:	Copyright © 2016 Nature America, Inc., part of Springer Nature. All rights reserved.
Official Publication:	https://doi.org/10.1038/ng.3709
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

Repository Staff Only: item control page