文章：

从发育角度看人类生殖细胞肿瘤

Human germ cell tumours from a developmental perspective

原文发布日期：2019-08-14

DOI: 10.1038/s41568-019-0178-9

类型: Review Article

开放获取: 否

英文摘要：

Human germ cell tumours (GCTs) are derived from stem cells of the early embryo and the germ line. They occur in the gonads (ovaries and testes) and also in extragonadal sites, where migrating primordial germ cells are located during embryogenesis. This group of heterogeneous neoplasms is unique in that their developmental potential is in effect determined by the latent potency state of their cells of origin, which are reprogrammed to omnipotent, totipotent or pluripotent stem cells. Seven GCT types, defined according to their developmental potential, have been identified, each with distinct epidemiological and (epi)genomic features. Heritable predisposition factors affecting the cells of origin and their niches likely explain bilateral, multiple and familial occurrences of the different types of GCTs. Unlike most other tumour types, GCTs are rarely caused by somatic driver mutations, but arise through failure to control the latent developmental potential of their cells of origin, resulting in their reprogramming. Consistent with their non-mutational origin, even the malignant tumours of the group are characterized by wild-type TP53 and high sensitivity for DNA damage. However, tumour progression and the rare occurrence of treatment resistance are driven by embryonic epigenetic state, specific (sub)chromosomal imbalances and somatic mutations. Thus, recent progress in understanding GCT biology supports a comprehensive developmental pathogenetic model for the origin of all GCTs, and provides new biomarkers, as well as potential targets for treatment of resistant disease.

摘要翻译： 

人类生殖细胞肿瘤（GCTs）起源于早期胚胎和生殖系的干细胞。这类肿瘤既可发生于性腺（卵巢与睾丸），也可出现在性腺外部位——即胚胎发生过程中原始生殖细胞迁移所处的位点。这类异质性肿瘤群体的独特之处在于，其发育潜能实际上是由起源细胞的潜在潜能状态决定的，这些细胞被重编程为全能性、全向性或多能性干细胞。根据发育潜能已界定出七种GCT亚型，每种都具有独特的流行病学特征和（表观）基因组学特征。影响起源细胞及其微环境的可遗传易感因素可能解释了不同类型GCT的双侧性、多发性及家族性发病现象。与大多数其他肿瘤类型不同，GCT很少由体细胞驱动突变引起，而是源于对起源细胞潜在发育潜能的控制失效，导致其发生重编程。与其非突变起源一致的是，即便是该类别中的恶性肿瘤也以TP53野生型和高DNA损伤敏感性为特征。然而，肿瘤进展及罕见的治疗耐药现象是由胚胎表观遗传状态、特异性（亚）染色体失衡及体细胞突变驱动的。因此，对GCT生物学机制的最新研究进展为所有GCT的起源提供了全面的发育病原学模型，并为耐药性疾病的治疗提供了新型生物标志物及潜在靶点。

原文链接：

Human germ cell tumours from a developmental perspective