Bruggeman Jan Willem, Irie Naoko, Lodder Paul, van Pelt Ans M M, Koster Jan, Hamer Geert
Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam Research Institute Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Cancers (Basel). 2020 Dec 17;12(12):3812. doi: 10.3390/cancers12123812.
We have recently described a class of 756 genes that are widely expressed in cancers, but are normally restricted to adult germ cells, referred to as germ cell cancer genes (GC genes). We hypothesized that carcinogenesis involves the reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17,382 samples from 54 healthy somatic tissues (GTEx) and 11,003 samples from 33 tumor types (TCGA), and identified 672 GC genes, expanding the known GC gene pool by 387 genes (51%). We found that GC genes are expressed in clusters that are often expressed in multiple tumor types. Moreover, the amount of GC gene expression correlates with poor survival in patients with lung adenocarcinoma. As GC genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC genes and may preserve fertility. We anticipate that our extended GC dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development.
我们最近描述了一类756个基因，它们在癌症中广泛表达，但通常仅限于成年生殖细胞，被称为生殖细胞癌基因（GC基因）。我们假设致癌作用涉及生物分子过程和调节机制的重新激活，而在正常情况下，这些过程和机制仅限于生殖系发育。这意味着癌细胞与原始生殖细胞（PGC）具有共同的基因表达谱。因此，我们将人类PGC（hPGC）和类PGC细胞（PGCLC）的转录组与来自54个健康体细胞组织（GTEx）的17382个样本以及来自33种肿瘤类型（TCGA）的11003个样本进行了比较，鉴定出672个GC基因，使已知的GC基因库增加了387个基因（51%）。我们发现GC基因以簇的形式表达，这些簇通常在多种肿瘤类型中表达。此外，GC基因的表达量与肺腺癌患者的不良生存相关。由于胚胎生殖系特有的GC基因在任何成年组织中都不表达，因此在癌症治疗中靶向这些基因可能比靶向传统的癌胚（CT）或GC基因产生更少的副作用，并且可能保留生育能力。我们预计，我们扩展的GC数据集能够增进对肿瘤发展的理解，并可能为癌症治疗开发提供多个新的靶点。
