The genomic landscape of core-binding factor acute myeloid leukemias.
The genomic landscape of core-binding factor acute myeloid leukemias.
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DOI：
10.1038/ng.3709
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发表时间：
2016-12
期刊：
影响因子：
30.8
通讯作者：
Downing JR
中科院分区：
文献类型：
--
作者：
Faber ZJ;Chen X;Gedman AL;Boggs K;Cheng J;Ma J;Radtke I;Chao JR;Walsh MP;Song G;Andersson AK;Dang J;Dong L;Liu Y;Huether R;Cai Z;Mulder H;Wu G;Edmonson M;Rusch M;Qu C;Li Y;Vadodaria B;Wang J;Hedlund E;Cao X;Yergeau D;Nakitandwe J;Pounds SB;Shurtleff S;Fulton RS;Fulton LL;Easton J;Parganas E;Pui CH;Rubnitz JE;Ding L;Mardis ER;Wilson RK;Gruber TA;Mullighan CG;Schlenk RF;Paschka P;Döhner K;Döhner H;Bullinger L;Zhang J;Klco JM;Downing JR
急性髓性白血病（AML）包括一组异质性白血病，通常定义为复发性细胞遗传学异常，包括涉及核心结合因子（CBF）转录复合物亚基的重排。为了更好地了解CBF-AML的基因组格局，我们通过全基因组或全外显子组测序分析了儿童（n=87）和成人（n=78）样本，包括RUNX 1-RUNX 1 T1（n=85）或CBFB-MYH 11（n=80）重排病例。除了先前报道的Ras信号通路中的体细胞突变之外，我们还鉴定了CCND 2中的复发性稳定突变，这表明CBF-AML中存在复发性和先前未被认识到的协作通路。除了信号改变之外，RUNX 1-RUNX 1 T1和CBFB-MYH 11 AML表现出明显不同的合作突变谱，因为RUNX 1-RUNX 1 T1病例在DHX 15和ZBTB 7A中携带复发性体细胞突变，以及在表观遗传调节因子（包括ASXL 2）和粘附素复合物组分中富集体细胞突变。这种详细的分析为CBF-AML的发病机制和发展提供了见解，同时突出了这些相关AML亚型之间合作突变的巨大差异。
Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving subunits of 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 previously reported somatic mutations in the Ras signaling pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a recurrent and previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated a remarkably different spectrum of cooperating mutations as RUNX1-RUNX1T1 cases harbored recurrent somatic mutations in DHX15 and ZBTB7A, as well as an enrichment of somatic mutations in epigenetic regulators, including ASXL2, and in components of the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscape of cooperating mutations between these related AML subtypes.
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影响因子：
11.4
作者：
Goemans, BF;Zwaan, CM;Heinrich, MC
通讯作者：
Heinrich, MC
影响因子：
9.8
作者：
Deardorff, Matthew A.;Kaur, Maninder;Krantz, Ian D.
通讯作者：
Krantz, Ian D.
DOI：
10.1084/jem.20131141
发表时间：
2013-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Abdel-Wahab O;Gao J;Adli M;Dey A;Trimarchi T;Chung YR;Kuscu C;Hricik T;Ndiaye-Lobry D;Lafave LM;Koche R;Shih AH;Guryanova OA;Kim E;Li S;Pandey S;Shin JY;Telis L;Liu J;Bhatt PK;Monette S;Zhao X;Mason CE;Park CY;Bernstein BE;Aifantis I;Levine RL
通讯作者：
Levine RL
影响因子：
11.2
作者：
Farrar JE;Schuback HL;Ries RE;Wai D;Hampton OA;Trevino LR;Alonzo TA;Guidry Auvil JM;Davidsen TM;Gesuwan P;Hermida L;Muzny DM;Dewal N;Rustagi N;Lewis LR;Gamis AS;Wheeler DA;Smith MA;Gerhard DS;Meshinchi S
通讯作者：
Meshinchi S
影响因子：
11.4
作者：
Bouchard, C;Thieke, K;Eilers, M
通讯作者：
Eilers, M