The epigenomics of sarcoma.
The epigenomics of sarcoma.
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DOI：
10.1038/s41568-020-0288-4
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Nielsen TO
中科院分区：
文献类型：
--
作者：
Nacev BA;Jones KB;Intlekofer AM;Yu JSE;Allis CD;Tap WD;Ladanyi M;Nielsen TO
表观遗传调控对发育、细胞命运、细胞增殖、基因组完整性以及转录调控的生理控制至关重要。这种表观遗传控制发生在多个层面，包括DNA甲基化、组蛋白修饰、核小体重塑和三维染色质结构的调节。编码染色质调节因子的基因改变在间充质肿瘤中很常见，间充质肿瘤是160多种肿瘤类型的集合，包括60多种恶性变异（肉瘤），它们具有独特而多样的遗传、生物学和临床特征。在这里，我们回顾了染色质通路改变驱动疾病生物学的肉瘤。具体来说，我们强调了每个水平的表观遗传控制失调的例子，其机制包括对调节DNA甲基化和组蛋白翻译后修饰的酶的代谢影响，组蛋白基因的突变，染色质重塑和修饰复合体的亚基丢失或融合，以及高阶染色质结构的破坏。肿瘤发生的表观遗传机制与间充质肿瘤有关，从成软骨细胞瘤和骨巨细胞瘤到软骨肉瘤、恶性周围神经鞘肿瘤、滑膜肉瘤、上皮样肉瘤和尤文氏肉瘤：这些侵袭性疾病比大多数癌症更容易出现在年轻的患者群体中。最后，基于对染色质失调的新认识，我们回顾了肉瘤治疗的当前和潜在的未来方法。
Epigenetic regulation is critical to physiologic control of development, cell fate, cell proliferation, genomic integrity, and fundamentally, transcriptional regulation. This epigenetic control occurs at multiple levels including through DNA methylation, histone modification, nucleosome remodeling, and modulation of three-dimensional chromatin structure. Alterations in genes that encode chromatin regulators are common among mesenchymal neoplasms, a collection of more than 160 tumor types including over 60 malignant variants (sarcomas) that have unique and varied genetic, biologic, and clinical characteristics. Here, we review sarcomas in which chromatin pathway alterations drive disease biology. Specifically, we emphasize examples of dysregulation of each level of epigenetic control though mechanisms that include metabolic effects on enzymes that regulate DNA methylation and histone posttranslational modification, mutations in histone genes, subunit loss or fusions in chromatin remodeling and modifying complexes, and disruption of higher-order chromatin structure. Epigenetic mechanisms of tumorigenesis have been implicated in mesenchymal tumors ranging from chondroblastoma and giant cell tumor of bone to chondrosarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma, epithelioid sarcoma and Ewing sarcoma: aggressive diseases which present in a younger patient population than most cancers. Finally, we review current and potential future approaches for the development of sarcoma therapies based on this emerging understanding of chromatin dysregulation.
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影响因子：
14.9
作者：
Arimura Y;Ikura M;Fujita R;Noda M;Kobayashi W;Horikoshi N;Sun J;Shi L;Kusakabe M;Harata M;Ohkawa Y;Tashiro S;Kimura H;Ikura T;Kurumizaka H
通讯作者：
Kurumizaka H
影响因子：
50.3
作者：
Banito A;Li X;Laporte AN;Roe JS;Sanchez-Vega F;Huang CH;Dancsok AR;Hatzi K;Chen CC;Tschaharganeh DF;Chandwani R;Tasdemir N;Jones KB;Capecchi MR;Vakoc CR;Schultz N;Ladanyi M;Nielsen TO;Lowe SW
通讯作者：
Lowe SW
影响因子：
10.5
作者：
Boulay G;Volorio A;Iyer S;Broye LC;Stamenkovic I;Riggi N;Rivera MN
通讯作者：
Rivera MN
影响因子：
64.5
作者：
Boija A;Klein IA;Sabari BR;Dall'Agnese A;Coffey EL;Zamudio AV;Li CH;Shrinivas K;Manteiga JC;Hannett NM;Abraham BJ;Afeyan LK;Guo YE;Rimel JK;Fant CB;Schuijers J;Lee TI;Taatjes DJ;Young RA
通讯作者：
Young RA
影响因子：
30.8
作者：
Behjati, Sam;Tarpey, Patrick S.;Presneau, Nadege;Scheipl, Susanne;Pillay, Nischalan;Van Loo, Peter;Wedge, David C.;Cooke, Susanna L.;Gundem, Gunes;Davies, Helen;Nik-Zainal, Serena;Martin, Sancha;McLaren, Stuart;Goodie, Victoria;Robinson, Ben;Butler, Adam;Teague, Jon W.;Halai, Dina;Khatri, Bhavisha;Myklebost, Ola;Baumhoer, Daniel;Jundt, Gernot;Hamoudi, Rifat;Tirabosco, Roberto;Amary, M. Fernanda;Futreal, P. Andrew;Stratton, Michael R.;Campbell, Peter J.;Flanagan, Adrienne M.
通讯作者：
Flanagan, Adrienne M.