Meta‐analysis of expression of l(3)mbt tumor‐associated germline genes supports the model that a soma‐to‐germline transition is a hallmark of human cancers

Evidence is starting to emerge indicating that tumorigenesis in metazoans involves a soma‐to‐germline transition, which may contribute to the acquisition of neoplastic characteristics. Here, we have meta‐analyzed gene expression profiles of the human orthologs of Drosophila melanogaster germline genes that are ectopically expressed in l(3)mbt brain tumors using gene expression datasets derived from a large cohort of human tumors. We find these germline genes, some of which drive oncogenesis in D. melanogaster, are similarly ectopically activated in a wide range of human cancers. Some of these genes normally have expression restricted to the germline, making them of particular clinical interest. Importantly, these analyses provide additional support to the emerging model that proposes a soma‐to‐germline transition is a general hallmark of a wide range of human tumors. This has implications for our understanding of human oncogenesis and the development of new therapeutic and biomarker targets with clinical potential. What's new? Although individual tumors are a complex mosaic of cells, subject to ongoing genetic and epigenetic change, evidence suggests that a general hallmark of human cancer is the development of tumors from a soma‐to‐germline transition. This meta‐analysis supports that idea, revealing that human genes that are orthologues of the oncogenic germline drivers of brain tumors in Drosophila melanogaster are activated in a wide range of human cancers. The findings have implications for the understanding of cancer and for the development of new therapeutic and diagnostic tools.