3D Chromatin Organization Group, Josep Carreras Leukaemia Research Institute (IJC), Germans Trias i Pujol, Badalona, Spain.
Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain.
Front Immunol. 2020 Oct 7;11:592087. doi: 10.3389/fimmu.2020.592087. eCollection 2020.
Associations between blood cancer and genetic predisposition, including both inherited variants and acquired mutations and epimutations, have been well characterized. However, the majority of these variants affect noncoding regions, making their mechanisms difficult to hypothesize and hindering the translation of these insights into patient benefits. Fueled by unprecedented progress in next-generation sequencing and computational integrative analysis, studies have started applying combinations of epigenetic, genome architecture, and functional assays to bridge the gap between noncoding variants and blood cancer. These complementary tools have not only allowed us to understand the potential malignant role of these variants but also to differentiate key variants, cell-types, and conditions from misleading ones. Here, we briefly review recent studies that have provided fundamental insights into our understanding of how noncoding mutations at enhancers predispose and promote blood malignancies in the context of spatial genome architecture.
血液癌症与遗传易感性之间的关联，包括遗传变异和获得性突变和表观遗传改变，已经得到了很好的描述。然而，这些变异中的大多数都影响非编码区域，这使得它们的机制难以假设，并阻碍了将这些见解转化为患者受益。受到下一代测序和计算综合分析的空前进展的推动，研究已经开始将表观遗传、基因组结构和功能分析组合应用于弥合非编码变异与血液癌症之间的差距。这些互补工具不仅使我们能够了解这些变异的潜在恶性作用，还能够区分关键的变异、细胞类型和条件与误导性的变异、细胞类型和条件。在这里，我们简要回顾了最近的研究，这些研究为我们理解增强子中非编码突变如何在空间基因组结构的背景下导致和促进血液恶性肿瘤提供了基本的见解。
