Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria.
OMICS Center Graz, BioTechMed Graz, Graz, Austria.
Andrology. 2019 Jul;7(4):415-427. doi: 10.1111/andr.12628. Epub 2019 May 17.
Germ cell tumours are uniquely associated with the gametogenic tissues of males and females. A feature of these cancers is that they can express genes that are normally tightly restricted to meiotic cells. This aberrant gene expression has been used as an indicator that these cancer cells are attempting a programmed germ line event, meiotic entry. However, work in non-germ cell cancers has also indicated that meiotic genes can become aberrantly activated in a wide range of cancer types and indeed provide functions that serve as oncogenic drivers. Here, we review the activation of meiotic factors in cancers and explore commonalities between meiotic gene activation in germ cell and non-germ cell cancers.
The objectives of this review are to highlight key questions relating to meiotic gene activation in germ cell tumours and to offer possible interpretations as to the biological relevance in this unique cancer type.
PubMed and the GEPIA database were searched for papers in English and for cancer gene expression data, respectively.
We provide a brief overview of meiotic progression, with a focus on the unique mechanisms of reductional chromosome segregation in meiosis I. We then offer detailed insight into the role of meiotic chromosome regulators in non-germ cell cancers and extend this to provide an overview of how this might relate to germ cell tumours.
We propose that meiotic gene activation in germ cell tumours might not indicate an unscheduled attempt to enter a full meiotic programme. Rather, it might simply reflect either aberrant activation of a subset of meiotic genes, with little or no biological relevance, or aberrant activation of a subset of meiotic genes as positive tumour evolutionary/oncogenic drivers. These postulates provide the provocation for further studies in this emerging field.
生殖细胞肿瘤与男性和女性的生殖细胞组织独特相关。这些癌症的一个特征是,它们可以表达通常严格局限于减数分裂细胞的基因。这种异常基因表达已被用作这些癌细胞正在尝试程序化生殖系事件(减数分裂进入)的指标。然而,非生殖细胞癌症的研究也表明,减数分裂基因可以在广泛的癌症类型中异常激活,并且实际上提供了作为致癌驱动因素的功能。在这里,我们回顾了减数分裂因子在癌症中的激活,并探讨了生殖细胞和非生殖细胞癌症中减数分裂基因激活的共同之处。
本综述的目的是强调与生殖细胞肿瘤中减数分裂基因激活相关的关键问题,并提供对这种独特癌症类型中生物学相关性的可能解释。
在 PubMed 和 GEPIA 数据库中分别用英文搜索论文和癌症基因表达数据。
我们简要概述了减数分裂进程,重点介绍了减数分裂 I 中减数分裂染色体分离的独特机制。然后,我们详细探讨了减数分裂染色体调节剂在非生殖细胞癌症中的作用,并将其扩展到如何与生殖细胞肿瘤相关的概述。
我们提出,生殖细胞肿瘤中减数分裂基因的激活可能并不表明不规律地试图进入完整的减数分裂程序。相反,它可能仅仅反映了减数分裂基因的子集异常激活,几乎没有或没有生物学相关性,或者减数分裂基因的子集异常激活作为积极的肿瘤进化/致癌驱动因素。这些假设为这一新兴领域的进一步研究提供了启示。