Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Martin, Slovakia
Department of Pathological Anatomy, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
Neoplasma. 2018;65(4):477-493. doi: 10.4149/neo_2018_170726N504.
Many diseases have different pathological backgrounds responsible for abnormal cell behavior and exhibiting altered function and signal transduction. This is especially true for tumors and although changes affecting DNA sequence, irreversible mutations and chromosomal aberrations in gastrointestinal stromal tumors (GISTs) have been widely studied, the importance of reversible epigenetic changes increasingly recognized in many cancers has received insufficient attention in these tumors. Epigenetic mechanisms are part of normal development and gene expression under normal conditions, but malfunction of these processes leads to malignant transformation by disturbing both intra- and intercellular communication. GISTs are a specific group of gastrointestinal tract tumors resistant to conventional chemotherapy and radiotherapy. Although they account for only 1% to 2% of tumors, they are among the most widespread gastrointestinal mesenchymal tumors. DNA hyper/hypomethylation overexpression/underexpression of miRNAs or abnormal histone modification may provide an alternative to the genetic modifications responsible for GIST pathology, response to treatment, prognosis and overall survival. This review summarizes the known epigenetic mechanisms involved in GIST pathogenesis; including onset, progression, and GISTs resistance. Reversible epigenetic changes are a novel and appropriate approach to halt the spread of metastases and the emergence of resistance in GIST treatment, and these changes depend on the type of epigenetic alternation, including inhibitors of histone acetyltranferase and deacetylase and DNA methyltransferases.
许多疾病都有不同的病理背景，这些背景导致异常的细胞行为，并表现出改变的功能和信号转导。这在肿瘤中尤其如此，尽管胃肠道间质瘤（GIST）中影响 DNA 序列、不可逆突变和染色体异常的改变已经得到了广泛研究，但在这些肿瘤中，许多癌症中越来越被认识到的可逆表观遗传变化的重要性却没有得到足够的重视。表观遗传机制是正常发育和正常条件下基因表达的一部分，但这些过程的功能障碍通过干扰细胞内和细胞间的通讯导致恶性转化。GIST 是一类对常规化疗和放疗具有耐药性的胃肠道特定肿瘤。尽管它们仅占肿瘤的 1%至 2%，但它们是最广泛的胃肠道间叶肿瘤之一。DNA 超/低甲基化、miRNA 的过表达/低表达或异常组蛋白修饰可能为 GIST 病理学、对治疗的反应、预后和总体生存中负责的遗传修饰提供替代方法。这篇综述总结了涉及 GIST 发病机制的已知表观遗传机制；包括发病、进展和 GIST 耐药性。可逆的表观遗传变化是阻止 GIST 治疗中转移扩散和耐药性出现的一种新的、合适的方法，这些变化取决于表观遗传改变的类型，包括组蛋白乙酰转移酶和去乙酰化酶以及 DNA 甲基转移酶的抑制剂。
