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Publication : The genomic landscape of core-binding factor acute myeloid leukemias.

First Author  Faber ZJ Year  2016
Journal  Nat Genet Volume  48
Issue  12 Pages  1551-1556
PubMed ID  27798625 Mgi Jnum  J:259250
Mgi Id  MGI:6141256 Doi  10.1038/ng.3709
Citation  Faber ZJ, et al. (2016) The genomic landscape of core-binding factor acute myeloid leukemias. Nat Genet 48(12):1551-1556
abstractText  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.
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