Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
Int J Mol Sci. 2019 Jan 10;20(2):258. doi: 10.3390/ijms20020258.
Current (high throughput omics-based) data support the model that human (malignant) germ cell tumors are not initiated by somatic mutations, but, instead through a defined locked epigenetic status, representative of their cell of origin. This elegantly explains the role of both genetic susceptibility as well as environmental factors in the pathogenesis, referred to as 'genvironment'. Moreover, it could also explain various epidemiological findings, including the rising incidence of this type of cancer in Western societies. In addition, it allows for identification of clinically relevant and informative biomarkers both for diagnosis and follow-up of individual patients. The current status of these findings will be discussed, including the use of high throughput DNA methylation profiling for determination of differentially methylated regions (DMRs) as well as chromosomal copy number variation (CNV). Finally, the potential value of methylation-specific tumor DNA fragments (i.e., promotor) as well as embryonic microRNAs as molecular biomarkers for cancer detection in liquid biopsies will be presented.
目前（基于高通量组学的）数据支持这样的模型，即人类（恶性）生殖细胞肿瘤不是由体细胞突变引发的，而是通过一种特定的、固定的表观遗传状态来代表其起源细胞。这巧妙地解释了遗传易感性和环境因素在发病机制中的作用，即“genvironment”。此外，它还可以解释各种流行病学发现，包括这种癌症在西方社会发病率的上升。此外，它还可以识别出临床相关且有意义的生物标志物，用于诊断和随访个体患者。本文将讨论这些发现的现状，包括使用高通量 DNA 甲基化分析来确定差异甲基化区域（DMR）和染色体拷贝数变异（CNV）。最后，将介绍甲基化特异性肿瘤 DNA 片段（即启动子）和胚胎 microRNAs 作为液体活检中癌症检测的分子生物标志物的潜在价值。
