The genomic landscape of core-binding factor acute myeloid leukemias

Lars Bullinger, Jinghui Zhang, Jeffery Klco, James Downing and colleagues report a detailed genomic analysis of pediatric and adult core-binding factor acute myeloid leukemias (CBF-AMLs). They identify recurrent mutations in CCND2 , MGA , DHX15 and ZBTB7A and highlight dramatic differences in the la...

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Vydané v:	Nature genetics Ročník 48; číslo 12; s. 1551 - 1556
Hlavní autori:	Faber, Zachary J, Chen, Xiang, Gedman, Amanda Larson, Boggs, Kristy, Cheng, Jinjun, Ma, Jing, Radtke, Ina, Chao, Jyh-Rong, Walsh, Michael P, Song, Guangchun, Andersson, Anna K, Dang, Jinjun, Dong, Li, Liu, Yu, Huether, Robert, Cai, Zhongling, Mulder, Heather, Wu, Gang, Edmonson, Michael, Rusch, Michael, Qu, Chunxu, Li, Yongjin, Vadodaria, Bhavin, Wang, Jianmin, Hedlund, Erin, Cao, Xueyuan, Yergeau, Donald, Nakitandwe, Joy, Pounds, Stanley B, Shurtleff, Sheila, Fulton, Robert S, Fulton, Lucinda L, Easton, John, Parganas, Evan, Pui, Ching-Hon, Rubnitz, Jeffrey E, Ding, Li, Mardis, Elaine R, Wilson, Richard K, Gruber, Tanja A, Mullighan, Charles G, Schlenk, Richard F, Paschka, Peter, Döhner, Konstanze, Döhner, Hartmut, Bullinger, Lars, Zhang, Jinghui, Klco, Jeffery M, Downing, James R
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.12.2016 Nature Publishing Group
Predmet:	631/208/514/1948 631/67/1990/283/1897 Adult Agriculture Analysis Animal Genetics and Genomics Bioinformatics Biomarkers, Tumor - genetics Biomedicine Biosynthesis Cancer Cancer genetics Cancer Research Child Children & youth Clinical Medicine Core Binding Factors - genetics Epigenetic inheritance Gene Function Genetic aspects Genomes Genomics Genomics - methods Hematologi Hematology Human Genetics Humans Klinisk medicin Laboratories letter Leukemia Leukemia, Myeloid, Acute - genetics Medical and Health Sciences Medicin och hälsovetenskap Mutation Mutation - genetics Oncogene Proteins, Fusion - genetics Pediatrics Proteins Spectrum analysis Studies Transcription (Genetics) Transcription factors
ISSN:	1061-4036, 1546-1718, 1546-1718
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Shrnutí:	Lars Bullinger, Jinghui Zhang, Jeffery Klco, James Downing and colleagues report a detailed genomic analysis of pediatric and adult core-binding factor acute myeloid leukemias (CBF-AMLs). They identify recurrent mutations in CCND2 , MGA , DHX15 and ZBTB7A and highlight dramatic differences in the landscape of cooperating mutations between different CBF-AML subtypes. 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.
Bibliografia:	SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work Current affiliation: Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.3709