PDF(Pubmed)
Abstract：
Germ cell tumors (GCTs) are relatively rare tumors. However, they are the most diagnosed malignancies occurring in the testis among men aged between 15 and 40 years. Despite high aneuploidy and a paucity of somatic mutations, several genomic and transcriptomic assays have identified a few significantly mutated somatic genes, primarily KIT and K-RAS. The receptor Tyrosine Kinase (RTK) pathway and the downstream related Mitogen-Activated Protein Kinase (MAPK) cascades are crucial signal transduction pathways that preside over various cellular processes, including proliferation, differentiation, apoptosis, and responses to stressors. They are well described in solid malignancies, where many of the involved factors are used as prognostic molecular markers or targets for precision therapy. This narrative review focused, in the first part, on PGCs\' survival/proliferation and differentiation and on the genetic and epigenetic factors involved in the pathogenesis of testicular germ cell tumors (TGCTs) and, in the second part, on the most recent investigations about the KIT-RAS pathway in TGCTs and in other cancers, highlighting the efforts that are being made to identify targetable markers for precision medicine approaches.
摘要：
生殖细胞肿瘤(GCTs)是相对罕见的肿瘤。然而,它们是15至40岁男性睾丸中诊断最多的恶性肿瘤。尽管高度非整倍性和缺乏体细胞突变，一些基因组和转录组分析已经确定了一些显著突变的体细胞基因，主要是KIT和K-RAS。受体酪氨酸激酶（RTK）途径和下游相关的丝裂原激活蛋白激酶（MAPK）级联是主持各种细胞过程的关键信号转导途径，包括扩散，分化,凋亡，以及对压力源的反应。它们在实体恶性肿瘤中有很好的描述，其中许多相关因素被用作精确治疗的预后分子标志物或靶标。这篇叙述性评论的重点是，在第一部分,关于PGCs的存活/增殖和分化以及涉及睾丸生殖细胞肿瘤（TGCT）发病机理的遗传和表观遗传因素，在第二部分,关于TGCT和其他癌症中KIT-RAS途径的最新研究，强调正在努力确定精准医学方法的目标标记。
