我们从表观遗传学的角度描述了融合驱动的肉瘤病因学的令人兴奋的最新进展。通过探索该领域的现状，我们确定并描述了决定肉瘤发生的核心机制。此外，我们讨论了翻译基因组学的开创性研究，这些研究使得融合驱动的肉瘤的表观遗传特征成为可能。表观遗传机制的重要背景包括但不限于细胞周期和代谢、核心调节电路、3维染色质结构失调、与ATP依赖性染色质重塑的整合以及转化动物模型。矛盾的是，虽然致癌转化的遗传要求对于融合伴侣来说是高度特异性的，但我们作为一个群体发现的表观遗传机制却非常广泛。这种二分法提出了一个问题：罕见疾病表观基因组学的研究是否应该优先研究个体细胞群，从而检查染色质失调的机制是否特定于特定肿瘤。我们回顾了横纹肌肉瘤、滑膜肉瘤、肺泡软组织肉瘤、透明细胞肉瘤、未分化圆形细胞肉瘤、尤文肉瘤、粘液样/圆形脂肪肉瘤、上皮样血管内皮瘤和促结缔组织增生性圆形细胞肿瘤的最新进展。该领域越来越多的突破性发现促使我们期待未来几年机械表观基因组学和直接靶向融合转录因子领域会取得进一步令人兴奋的进展。版权所有 © 2024 Stanton 和 Pomella。

We describe exciting recent advances in fusion-driven sarcoma etiology, from an epigenetics perspective. By exploring the current state of the field, we identify and describe the central mechanisms that determine sarcomagenesis. Further, we discuss seminal studies in translational genomics, which enabled epigenetic characterization of fusion-driven sarcomas. Important context for epigenetic mechanisms include, but are not limited to, cell cycle and metabolism, core regulatory circuitry, 3-dimensional chromatin architectural dysregulation, integration with ATP-dependent chromatin remodeling, and translational animal modeling. Paradoxically, while the genetic requirements for oncogenic transformation are highly specific for the fusion partners, the epigenetic mechanisms we as a community have uncovered are categorically very broad. This dichotomy prompts the question of whether the investigation of rare disease epigenomics should prioritize studying individual cell populations, thereby examining whether the mechanisms of chromatin dysregulation are specific to a particular tumor. We review recent advances focusing on rhabdomyosarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, undifferentiated round cell sarcoma, Ewing sarcoma, myxoid/round liposarcoma, epithelioid hemangioendothelioma and desmoplastic round cell tumor. The growing number of groundbreaking discoveries in the field, motivated us to anticipate further exciting advances in the area of mechanistic epigenomics and direct targeting of fusion transcription factors in the years ahead.Copyright © 2024 Stanton and Pomella.