卵巢透明细胞癌中的表观遗传合成致死性：EZH2和ARID1A突变
Epigenetic synthetic lethality in ovarian clear cell carcinoma: EZH2 and ARID1A mutations.
作者信息
Bitler Benjamin G, Aird Katherine M, Zhang Rugang
机构信息
Gene Expression and Regulation, The Wistar Institute ; Philadelphia, PA USA.
出版信息
Mol Cell Oncol. 2015 Apr 14;3(1):e1032476. doi: 10.1080/23723556.2015.1032476. eCollection 2016 Jan.
Abstract
The components of the Switch/Sucrose non-fermentable (SWI/SNF) complex are mutated in approximately 20% of human cancers. The A/T-rich interacting domain 1A (ARID1A) subunit has one of the highest mutation rates. Most notably, ARID1A is mutated in over 50% of ovarian clear cell carcinomas (OCCCs). We reported that inhibition of enhancer of zeste homology 2 (EZH2) is synthetically lethal in ARID1A-mutated OCCC.
摘要
在大约20%的人类癌症中，开关/蔗糖非发酵（SWI/SNF）复合体的组件发生了突变。富含A/T的相互作用结构域1A（ARID1A）亚基的突变率最高。最值得注意的是，超过50%的卵巢透明细胞癌（OCCC）中ARID1A发生了突变。我们报道，在ARID1A突变的OCCC中，抑制zeste同源物2（EZH2）增强子具有合成致死性。
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本文引用的文献
1
Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers.通过靶向ARID1A突变癌症中的EZH2甲基转移酶活性实现合成致死
Nat Med. 2015 Mar;21(3):231-8. doi: 10.1038/nm.3799. Epub 2015 Feb 16.
2
Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling.ARID1A-PIK3CA共突变通过促肿瘤炎症细胞因子信号传导促进卵巢透明细胞肿瘤发生。
Nat Commun. 2015 Jan 27;6:6118. doi: 10.1038/ncomms7118.
3
Discovery and saturation analysis of cancer genes across 21 tumour types.在 21 种肿瘤类型中发现和饱和分析癌症基因。
Nature. 2014 Jan 23;505(7484):495-501. doi: 10.1038/nature12912. Epub 2014 Jan 5.
4
Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2.通过抑制甲基转移酶 EZH2，使基因改变的恶性横纹肌样肿瘤持久消退。
Proc Natl Acad Sci U S A. 2013 May 7;110(19):7922-7. doi: 10.1073/pnas.1303800110. Epub 2013 Apr 25.
5
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.EZH2 抑制作为 EZH2 激活突变淋巴瘤的治疗策略。
Nature. 2012 Dec 6;492(7427):108-12. doi: 10.1038/nature11606. Epub 2012 Oct 10.
6
Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation.抑癌基因与癌基因的表达调控
Cancer Cell. 2010 Oct 19;18(4):316-28. doi: 10.1016/j.ccr.2010.09.006.
7
ARID1A mutations in endometriosis-associated ovarian carcinomas.ARID1A 突变与子宫内膜异位症相关的卵巢癌。
N Engl J Med. 2010 Oct 14;363(16):1532-43. doi: 10.1056/NEJMoa1008433. Epub 2010 Sep 8.
8
Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma.卵巢透明细胞癌中染色质重塑基因 ARID1A 的频繁突变。
Science. 2010 Oct 8;330(6001):228-31. doi: 10.1126/science.1196333. Epub 2010 Sep 8.
9
The concept of synthetic lethality in the context of anticancer therapy.抗癌治疗背景下的合成致死概念。
Nat Rev Cancer. 2005 Sep;5(9):689-98. doi: 10.1038/nrc1691.
10
Expression of p270 (ARID1A), a component of human SWI/SNF complexes, in human tumors.人SWI/SNF复合物的组成成分p270（ARID1A）在人类肿瘤中的表达。
Int J Cancer. 2004 Nov 20;112(4):636. doi: 10.1002/ijc.20450.
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