Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia.
Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia.
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DOI：
10.1038/ncomms4469
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发表时间：
2014-03-24
影响因子：
16.6
通讯作者：
Armstrong, Scott A.
中科院分区：
文献类型：
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作者：
Mar, Brenton G.;Bullinger, Lars B.;McLean, Kathleen M.;Grauman, Peter V.;Harris, Marian H.;Stevenson, Kristen;Neuberg, Donna S.;Sinha, Amit U.;Sallan, Stephen E.;Silverman, Lewis B.;Kung, Andrew L.;Lo Nigro, Luca;Ebert, Benjamin L.;Armstrong, Scott A.
复发性小儿急性淋巴细胞白血病（ALL）的治疗失败率很高。表观遗传调节因子被认为是化疗耐药性的调节因子，在此我们对匹配的诊断-缓解-复发ALL样本中编码表观遗传调节因子的基因进行测序。我们发现在复发时表观遗传调节因子中的突变显著富集，其中在SETD 2、CREBBP、MSH 6、KDM 6A和MLL 2中具有复发性体细胞突变，而在信号传导因子中的突变不富集。在一个大型的原发ALL患者队列中，12%的患者存在SETD 2的体细胞改变，包括移码和无义突变。我们的结论是，在复发的表观遗传调节突变的富集是一致的，在介导治疗耐药性的作用。
Relapsed pediatric acute lymphoblastic leukemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here we sequence genes encoding epigenetic regulators in matched diagnosis-remission-relapse ALL samples. We find significant enrichment of mutations in epigenetic regulators at relapse with recurrent somatic mutations in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signaling factors are not enriched. Somatic alterations in SETD2, including frameshift and nonsense mutations, are present at 12% in a large de novo ALL patient cohort. We conclude that the enrichment of mutations in epigenetic regulators at relapse is consistent with a role in mediating therapy resistance.
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影响因子：
30.8
作者：
Meyer, Julia A.;Wang, Jinhua;Hogan, Laura E.;Yang, Jun J.;Dandekar, Smita;Patel, Jay P.;Tang, Zuojian;Zumbo, Paul;Li, Sheng;Zavadil, Jiri;Levine, Ross L.;Cardozo, Timothy;Hunger, Stephen P.;Raetz, Elizabeth A.;Evans, William E.;Morrison, Debra J.;Mason, Christopher E.;Carroll, William L.
通讯作者：
Carroll, William L.
影响因子：
30.8
作者：
Holmfeldt, Linda;Wei, Lei;Diaz-Flores, Ernesto;Walsh, Michael;Zhang, Jinghui;Ding, Li;Payne-Turner, Debbie;Churchman, Michelle;Andersson, Anna;Chen, Shann-Ching;McCastlain, Kelly;Becksfort, Jared;Ma, Jing;Wu, Gang;Patel, Samir N.;Heatley, Susan L.;Phillips, Letha A.;Song, Guangchun;Easton, John;Parker, Matthew;Chen, Xiang;Rusch, Michael;Boggs, Kristy;Vadodaria, Bhavin;Hedlund, Erin;Drenberg, Christina;Baker, Sharyn;Pei, Deqing;Cheng, Cheng;Huether, Robert;Lu, Charles;Fulton, Robert S.;Fulton, Lucinda L.;Tabib, Yashodhan;Dooling, David J.;Ochoa, Kerri;Minden, Mark;Lewis, Ian D.;To, L. Bik;Marlton, Paula;Roberts, Andrew W.;Raca, Gordana;Stock, Wendy;Neale, Geoffrey;Drexler, Hans G.;Dickins, Ross A.;Ellison, David W.;Shurtleff, Sheila A.;Pui, Ching-Hon;Ribeiro, Raul C.;Devidas, Meenakshi;Carroll, Andrew J.;Heerema, Nyla A.;Wood, Brent;Borowitz, Michael J.;Gastier-Foster, Julie M.;Raimondi, Susana C.;Mardis, Elaine R.;Wilson, Richard K.;Downing, James R.;Hunger, Stephen P.;Loh, Mignon L.;Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.
影响因子：
82.9
作者：
通讯作者：
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影响因子：
82.9
作者：
通讯作者：
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影响因子：
8
作者：
Spiegel, S.;Milstien, S.;Grant, S.
通讯作者：
Grant, S.