Faculty of Health Sciences, OsloMet - Oslo Metropolitan University, Oslo, Norway.
Department of Molecular Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Andrology. 2019 Jul;7(4):527-535. doi: 10.1111/andr.12663.
Testicular germ cell tumour (TGCT) is a malignancy with a high heritable component. The inherited risk is polygenic, and around 50 susceptibility genes are identified. The functional role of the gene products for TGCT development is not well understood. The focus of this review is functional studies of genetic risk factors for TGCT derived from GCNIS and the signalling pathways involved in the pathogenesis.
Genome-wide association studies have identified new risk loci for TGCT and confirmed previously identified susceptibility genes. Many of these risk genes are related to male germ cell development, sex determination and genomic integrity. Gain- and loss-of-function studies in animal models and TGCT cell lines, as well as gene and protein expression studies in TGCT patient samples, have contributed to the understanding of TGCT development. KITLG-KIT signalling is of crucial importance, but several other signal transduction pathways may also play a role. Many of the risk loci are in non-coding regions, and studies have revealed that non-coding RNAs may act as oncogenes or tumour suppressors in TGCT development.
The risk of TGCT is polygenic, and the underlying molecular mechanisms are complex. Several signalling pathways are related to TGCT development, and both proteins and non-coding RNAs may act as oncogenes or tumour suppressors. Epigenetic studies are of importance to get further knowledge about how the signalling pathways are regulated.
睾丸生殖细胞肿瘤（TGCT）是一种具有高遗传性成分的恶性肿瘤。遗传风险是多基因的，已经确定了约 50 个易感基因。这些基因产物在 TGCT 发展中的功能作用尚未得到很好的理解。本综述的重点是源自 GCNIS 的 TGCT 遗传风险因素的功能研究以及发病机制中涉及的信号通路。
全基因组关联研究已经确定了 TGCT 的新风险位点，并证实了先前确定的易感基因。这些风险基因中的许多与男性生殖细胞发育、性别决定和基因组完整性有关。动物模型和 TGCT 细胞系中的功能获得和功能丧失研究，以及 TGCT 患者样本中的基因和蛋白表达研究，都有助于了解 TGCT 的发展。KITLG-KIT 信号传导至关重要，但其他几个信号转导通路也可能发挥作用。许多风险位点位于非编码区域，研究表明非编码 RNA 可能在 TGCT 发展中作为癌基因或肿瘤抑制因子发挥作用。
TGCT 的风险是多基因的，其潜在的分子机制很复杂。几个信号通路与 TGCT 的发展有关，蛋白质和非编码 RNA 都可能作为癌基因或肿瘤抑制因子发挥作用。表观遗传学研究对于进一步了解信号通路的调控方式很重要。
