Maleszewska Marta, Wojtas Bartosz, Kamińska Bożena
Instytut Biologii Doświadczalnej PAN im. M. Nenckiego w Warszawie.
Postepy Biochem. 2018 Oct 15;64(2):148-156. doi: 10.18388/pb.2018_125.
Gene expression of both normal and cancer cell is tightly regulated by specific transcription regulators and epigenetic mechanisms such as DNA methylation, histone modifications (acetylation, methylation, phosphorylation), nucleosome remodeling and non-coding RNAs. Deregulation of epigenetic mechanisms plays a pivotal role in cancer, although researchers debate if it is a cause or a consequence of oncogenic transformation. Independently from the way in which epigenetic alterations arise in cancer, downstream effects will result in profound changes in transcriptomic and subsequently proteomic profiles. In most cases, changes in expression of epigenetic genes produce functional advantages in cell proliferation, tumor growth and/or migration capacity. Most of epigenetic changes in cancer are triggered by genomic alterations in specific genes that are involved in controlling one of the epigenetic mechanisms. However, there are also mutations in cell metabolism-related genes that affect activities of DNA demethylating enzymes and histone modifiers. Histone modifications are deregulated in cancer mostly due to alterations in genes coding for enzymes that attach or remove histone modifications. Mutations in genes coding for nucleosome remodelers result in aberrant global chromatin organization and facilitate subsequent global alterations of gene copy number or translocations. Recent advancements in next generation sequencing allowed for more precise mapping of global changes in the epigenetic landscape in cancer.
正常细胞和癌细胞的基因表达都受到特定转录调节因子和表观遗传机制的严格调控，这些机制包括DNA甲基化、组蛋白修饰（乙酰化、甲基化、磷酸化）、核小体重塑和非编码RNA。表观遗传机制的失调在癌症中起着关键作用，尽管研究人员对于它是致癌转化的原因还是结果存在争议。无论癌症中表观遗传改变是如何产生的，其下游效应都会导致转录组以及随后的蛋白质组图谱发生深刻变化。在大多数情况下，表观遗传基因表达的变化在细胞增殖、肿瘤生长和/或迁移能力方面产生功能优势。癌症中的大多数表观遗传变化是由参与控制一种表观遗传机制的特定基因的基因组改变引发的。然而，也存在与细胞代谢相关基因的突变，这些突变会影响DNA去甲基化酶和组蛋白修饰酶的活性。组蛋白修饰在癌症中失调主要是由于编码连接或去除组蛋白修饰的酶的基因发生改变。编码核小体重塑蛋白的基因突变会导致异常的全局染色质组织，并促进随后基因拷贝数的全局改变或易位。新一代测序技术的最新进展使得能够更精确地绘制癌症表观遗传景观的全局变化图谱。
