Department of Obstestrics and Gynecology, School of Medicine, University of Patras, Patras,Greece.
Department of Pathology, School of Medicine, University of Patras, Patras,Greece.
Curr Mol Pharmacol. 2021;14(6):1013-1027. doi: 10.2174/1874467213666200810141858.
Ovarian cancer is an aggressive disease, and only a few cases are diagnosed at early stages due to the absence of symptoms. Τhe majority of malignant ovarian tumors (>90%) are of epithelial origin and are subdivided into five histological sub types according to different molecular pathogenesis and clinical behavior. High-grade serous ovarian cancer is the most common subtype (70%). However, the different histotypes of ovarian cancer should be viewed as separate diseases both clinically and in biomarker studies. At present, surgical debulking and platinum/taxane - based chemotherapy is the standard of care for epithelial ovarian cancer. Most patients show an initial response to this therapeutic approach, but the majority of them experience disease recurrence at which point cure is no longer possible, due to acquired resistance in those chemotherapeutic regimens. Nevertheless, the current treatment model is still a "one-sizefits- all" approach. Epigenetic modifications represent heritable modifications in gene expression without alteration of the DNA sequence. DNA methylation is the best-studied epigenetic mechanism, and in epithelial ovarian cancer, the methylenome is widely altered. In addition, patterns of DNA methylation may represent potential diagnostic and prognostic markers as well as markers predictive of chemoresistance and potential therapeutic targets. This article systematically reviews the complex area of DNA methylation in ovarian carcinoma and summarizes the current implications and future perspectives of its use as a screening, diagnostic, prognostic and predictive tool as well as in personalized cancer therapy.
卵巢癌是一种侵袭性疾病，由于缺乏症状，只有少数病例在早期被诊断出来。大多数恶性卵巢肿瘤（>90%）来源于上皮组织，并根据不同的分子发病机制和临床行为分为五种组织学亚型。高级别浆液性卵巢癌是最常见的亚型（70%）。然而，不同组织学类型的卵巢癌在临床和生物标志物研究中应被视为独立的疾病。目前，手术去瘤和铂类/紫杉醇为基础的化疗是上皮性卵巢癌的标准治疗方法。大多数患者对这种治疗方法有初始反应，但大多数患者在疾病复发时，由于对这些化疗方案产生获得性耐药，治愈已不再可能。然而，目前的治疗模式仍然是一种“一刀切”的方法。表观遗传修饰是指基因表达的可遗传修饰，而不改变 DNA 序列。DNA 甲基化是研究最充分的表观遗传机制，在上皮性卵巢癌中，甲基化组广泛改变。此外，DNA 甲基化模式可能代表潜在的诊断和预后标志物，以及预测化疗耐药性和潜在治疗靶点的标志物。本文系统地综述了卵巢癌中 DNA 甲基化的复杂领域，并总结了其作为筛查、诊断、预后和预测工具以及个性化癌症治疗中的当前意义和未来前景。
