Lee Maxwell P
High Dimension Data Analysis Group, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Front Oncol. 2019 Aug 21;9:794. doi: 10.3389/fonc.2019.00794. eCollection 2019.
Epigenetic information is characterized by its stable transmission during mitotic cell divisions and plasticity during development and differentiation. This duality is in contrast to genetic information, which is stable and identical in all cells in an organism with exception of immunoglobulin gene rearrangements in lymphocytes and somatic mutations in cancer cells. Allele-specific analysis of gene expression and epigenetic modifications provides a unique approach to studying epigenetic regulation in normal and cancer cells. Extension of Knudson's two-hits theory to include epigenetic alteration as a means to inactivate tumor suppressor genes provides better understanding of how genetic mutations and epigenetic alterations jointly contribute to cancer development. High-throughput technology has greatly accelerated cancer discovery. Large initiatives such as TCGA have shown that epigenetic components are frequent targets of mutations in cancer and these discoveries provide new insights into understanding cancer etiology and generate new opportunities for cancer therapeutics.
表观遗传信息的特点是在有丝分裂细胞分裂过程中稳定传递，而在发育和分化过程中具有可塑性。这种双重性与遗传信息形成对比，遗传信息在生物体的所有细胞中是稳定且相同的，淋巴细胞中的免疫球蛋白基因重排和癌细胞中的体细胞突变除外。基因表达和表观遗传修饰的等位基因特异性分析为研究正常细胞和癌细胞中的表观遗传调控提供了独特的方法。将克努森的双击理论扩展到包括表观遗传改变作为使肿瘤抑制基因失活的一种手段，有助于更好地理解基因突变和表观遗传改变如何共同促进癌症发展。高通量技术极大地加速了癌症的发现。诸如癌症基因组图谱（TCGA）之类的大型项目表明，表观遗传成分是癌症中突变的常见靶点，这些发现为理解癌症病因提供了新的见解，并为癌症治疗带来了新的机会。
