Rivera-Reyes Adrian, Hayer Katharina E, Bassing Craig H
Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Trends Mol Med. 2016 Dec;22(12):1035-1046. doi: 10.1016/j.molmed.2016.10.004. Epub 2016 Oct 27.
It has been appreciated for decades that somatic genomic alterations that change coding sequences of proto-oncogenes, translocate enhancers/promoters near proto-oncogenes, or create fusion oncogenes can drive cancer by inducing oncogenic activities. An explosion of genome-wide technologies over the past decade has fueled discoveries of the roles of three-dimensional chromosome structure and powerful cis-acting elements (super-enhancers) in regulating gene transcription. In recent years, studies of human T cell acute lymphoblastic leukemia (T-ALL) using genome-wide technologies have provided paradigms for how non-coding genomic region alterations can disrupt 3D chromosome architecture or establish super-enhancers to activate oncogenic transcription of proto-oncogenes. These studies raise important issues to consider with the objective of leveraging basic knowledge into new diagnostic and therapeutic opportunities for cancer patients.
几十年来，人们已经认识到，改变原癌基因编码序列、将增强子/启动子易位至原癌基因附近或产生融合癌基因的体细胞基因组改变，可通过诱导致癌活性驱动癌症发生。过去十年中，全基因组技术的迅猛发展推动了对三维染色体结构和强大的顺式作用元件（超级增强子）在调节基因转录中作用的发现。近年来，利用全基因组技术对人类T细胞急性淋巴细胞白血病（T-ALL）的研究，为非编码基因组区域改变如何破坏三维染色体结构或建立超级增强子以激活原癌基因的致癌转录提供了范例。这些研究提出了一些重要问题，旨在将基础知识转化为癌症患者新的诊断和治疗机会。
