Cancer Epigenetics Laboratory at the Cancer Cell Biology Group, Institut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain.
Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.
Cell Mol Life Sci. 2024 Jun 20;81(1):274. doi: 10.1007/s00018-024-05314-z.
Discoveries in the field of genomics have revealed that non-coding genomic regions are not merely "junk DNA", but rather comprise critical elements involved in gene expression. These gene regulatory elements (GREs) include enhancers, insulators, silencers, and gene promoters. Notably, new evidence shows how mutations within these regions substantially influence gene expression programs, especially in the context of cancer. Advances in high-throughput sequencing technologies have accelerated the identification of somatic and germline single nucleotide mutations in non-coding genomic regions. This review provides an overview of somatic and germline non-coding single nucleotide alterations affecting transcription factor binding sites in GREs, specifically involved in cancer biology. It also summarizes the technologies available for exploring GREs and the challenges associated with studying and characterizing non-coding single nucleotide mutations. Understanding the role of GRE alterations in cancer is essential for improving diagnostic and prognostic capabilities in the precision medicine era, leading to enhanced patient-centered clinical outcomes.
基因组学领域的发现揭示了非编码基因组区域并非仅仅是“垃圾 DNA”，而是包含了参与基因表达的关键元件。这些基因调控元件（GREs）包括增强子、绝缘子、沉默子和基因启动子。值得注意的是，新的证据表明，这些区域内的突变如何极大地影响基因表达程序，特别是在癌症的背景下。高通量测序技术的进步加速了非编码基因组区域中体细胞和种系单核苷酸突变的鉴定。这篇综述概述了影响 GRE 中转录因子结合位点的体细胞和种系非编码单核苷酸改变，特别是涉及癌症生物学的改变。它还总结了可用于探索 GRE 的技术以及研究和表征非编码单核苷酸突变所面临的挑战。了解 GRE 改变在癌症中的作用对于提高精准医学时代的诊断和预后能力至关重要，从而实现以患者为中心的临床结局的改善。
