期刊
NATURE GENETICS
卷 48, 期 12, 页码 1551-1556出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3709
关键词
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资金
- St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project
- American Lebanese and Syrian Associated Charities of St. Jude Children's Research Hospital
- US National Institutes of Health [P30 CA021765, K08 HL116605]
- Burroughs Wellcome Fund
- German Bundesministerium fur Bildung and Forschung (BMBF) [01GI9981, 01KG0605]
- Deutsche Krebshilfe [111911]
- Deutsche Forschungsgemeinschaft (DFG) [DO 704/3-1]
- DFG [SFB 1074]
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-RUNX1 T1 (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-RUNXIT1 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.
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