Germ cell tumours (GCTs) are a collection of benign and malignant neoplasms derived from primordial germ cells. They are uniquely able to recapitulate embryonic and extraembryonic tissues, which carries prognostic and therapeutic significance. The developmental pathways underpinning GCT initiation and histogenesis are incompletely understood. Here, we study the relationship of histogenesis and clonal diversification in GCTs by analysing the genomes and transcriptomes of 547 microdissected histological units. We find no correlation between genomic and histological heterogeneity. However, we identify unifying features including the retention of fetal developmental transcripts across tissues, expression changes on chromosome 12p, and a conserved somatic evolutionary sequence of whole genome duplication followed by clonal diversification. While this pattern is preserved across all GCTs, the developmental timing of the duplication varies between prepubertal and postpubertal cases. In addition, tumours of younger children exhibit distinct substitution signatures which may lend themselves as potential biomarkers for risk stratification. Our findings portray the extensive diversification of GCT tissues and genetic subclones as randomly distributed, while identifying overarching transcriptional and genomic features.

生殖细胞肿瘤（GCT）是源自原始生殖细胞的良性和恶性肿瘤的集合。它们具有独特的能力来重现胚胎和胚胎外组织，这具有预后和治疗意义。支持 GCT 启动和组织发生的发育途径尚不完全清楚。在这里，我们通过分析 547 个显微解剖组织学单位的基因组和转录组来研究 GCT 中组织发生和克隆多样化的关系。我们发现基因组异质性和组织学异质性之间没有相关性。然而，我们确定了统一的特征，包括跨组织的胎儿发育转录本的保留、12p 染色体上的表达变化以及全基因组复制随后克隆多样化的保守体细胞进化序列。虽然所有 GCT 中都保留了这种模式，但青春期前和青春期后病例之间重复的发育时间有所不同。此外，年幼儿童的肿瘤表现出独特的替代特征，这可能使其成为风险分层的潜在生物标志物。我们的研究结果描绘了随机分布的 GCT 组织和遗传亚克隆的广泛多样化，同时确定了总体转录和基因组特征。