Gorse Marine, Bianchi Charline, Proudhon Charlotte
Université de Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) UMR_S 1085, Rennes, France.
Med Sci (Paris). 2024 Dec;40(12):925-934. doi: 10.1051/medsci/2024180. Epub 2024 Dec 20.
Alterations in DNA methylation profiles are typically found in cancer cells, combining genome-wide hypomethylation with hypermethylation of specific regions, such as CpG islands, which are normally unmethylated. Driving effects in cancer development have been associated with alteration of DNA methylation in certain regions, inducing, for example, the repression of tumor suppressor genes or the activation of oncogenes and retrotransposons. These alterations represent prime candidates for the development of specific markers for the detection, diagnosis and prognosis of cancer. In particular, these markers, distributed along the genome, provide a wealth of information that offers potential for innovation in the field of liquid biopsy, in particular thanks to the emergence of artificial intelligence for diagnostic purposes. This could overcome the limitations related to sensitivities and specificities, which remain too low for the most difficult applications in oncology: the detection of cancers at an early stage, the monitoring of residual disease and the analysis of brain tumors. In addition, targeting the enzymatic processes that control the epigenome offers new therapeutic strategies that could reverse the regulatory anomalies of these altered epigenomes.
DNA甲基化谱的改变通常在癌细胞中被发现,其特点是全基因组低甲基化与特定区域(如通常未甲基化的CpG岛)的高甲基化相结合。癌症发展中的驱动效应与某些区域的DNA甲基化改变有关,例如,可诱导肿瘤抑制基因的抑制或癌基因及逆转座子的激活。这些改变是开发癌症检测、诊断和预后特异性标志物的主要候选对象。特别是,这些分布于基因组的标志物提供了丰富的信息,为液体活检领域的创新带来了潜力,尤其是得益于用于诊断目的的人工智能的出现。这可以克服与灵敏度和特异性相关的局限性,而这些局限性在肿瘤学中最具挑战性的应用(早期癌症检测、残留疾病监测和脑肿瘤分析)中仍然过低。此外,针对控制表观基因组的酶促过程提供了新的治疗策略,可逆转这些改变的表观基因组的调控异常。