文章：

肉瘤的表观基因组学

The epigenomics of sarcoma

原文发布日期：2020-08-11

DOI: 10.1038/s41568-020-0288-4

类型: Review Article

开放获取: 否

英文摘要：

Epigenetic regulation is critical to physiological 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 remodelling and modulation of the 3D chromatin structure. Alterations in genes that encode chromatin regulators are common among mesenchymal neoplasms, a collection of more than 160 tumour types including over 60 malignant variants (sarcomas) that have unique and varied genetic, biological and clinical characteristics. Herein, we review those 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 alterations in metabolic enzymes that regulate DNA methylation and histone post-translational modifications, mutations in histone genes, subunit loss or fusions in chromatin remodelling and modifying complexes, and disruption of higher-order chromatin structure. Epigenetic mechanisms of tumorigenesis have been implicated in mesenchymal tumours ranging from chondroblastoma and giant cell tumour of bone to chondrosarcoma, malignant peripheral nerve sheath tumour, synovial sarcoma, epithelioid sarcoma and Ewing sarcoma — all diseases that 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.

摘要翻译： 

表观遗传调控对于发育、细胞命运、细胞增殖、基因组完整性及转录调控等生理过程至关重要。这种表观遗传控制存在于多个层面，包括DNA甲基化、组蛋白修饰、核小体重塑以及三维染色质结构的调控。在间叶源性肿瘤中，编码染色质调控因子的基因改变十分常见。这类肿瘤包含160多种类型，其中有60多种恶性亚型（肉瘤），具有独特而多样的遗传学、生物学及临床特征。本文重点综述了染色质通路异常驱动疾病生物学机制的肉瘤类型。具体而言，我们通过以下机制阐述了各层级表观遗传控制的失调案例：调控DNA甲基化和组蛋白翻译后修饰的代谢酶改变、组蛋白基因突变、染色质重塑和修饰复合体的亚基缺失或融合，以及高级染色质结构的破坏。从软骨母细胞瘤、骨巨细胞瘤到软骨肉瘤、恶性外周神经鞘膜瘤、滑膜肉瘤、上皮样肉瘤和尤文氏肉瘤等一系列间叶源性肿瘤中，均发现了表观遗传的致癌机制——这些疾病均好发于较大多数癌症患者更年轻的群体。最后，基于对染色质失调机制的新认识，我们回顾了当前及未来潜在的肉瘤治疗策略开发路径。

原文链接：

The epigenomics of sarcoma