The aberrant expression of germline-specific genes in somatic tumors has been observed in multiple human cancers; these are genes for which normal expression is restricted to male or female germline cells or for which expression is highly biased to germline cells. The products of these genes are of particular interest for targeted therapies, since normal somatic cells are less likely to be impacted.
In Drosophila, screens for loss-of-function suppressors of the malignant brain tumor phenotype of Dmel\l(3)mbt (see the human disease model report 'cancer, neural stem cell, L3MBTL-related' FBhh0000773) have identified multiple germline-specific or germline-biased genes. These include mei-W68 (human SPO11), tud (human TDRD6), nos (human NANOS1, 2, 3), vas (human DDX4), piwi and aub (human PIWIL1, 2, 3, 4).
Drosophila testis-specific paralogs of proteins that translocate nuclearly-encoded mitochondrial proteins into mitochondria have been studied in this context. Translocases of outer membrane (tomboy20, ortholog of human TIMM50) and inner membrane (ttm2, ortholog of human TOMM20 and TOMM20L) complexes have been assessed. Expression in somatic epithelia of either tomboy20 or ttm2 results in tumorigenic phenotypes. In wing imaginal discs, significant overgrowth is observed and appears to be non-autonomous. In comparable experiments using Tom20, the somatic paralog of tomboy20, overgrowth phenotypes are not observed.
[updated Nov. 2020 by FlyBase; FBrf0222196]
Originally described as cancer/testis antigens, the aberrant expression of germline genes in somatic tumors has been observed in multiple human cancers (Feichtinger et al., 2012; pubmed:22918178; Feichtinger et al., 2014; pubmed:24243547; McFarlane et al., 2014; pubmed:25111983).
High-scoring ortholog of human SPO11 (1 Drosophila to 1 human). Dmel\mei-W68 shares 32% identity and 53% similarity with the human gene.
Low- to moderate-scoring ortholog of human TDRD6 and TDRD15 (1 Drosophila to 2 human). Dmel\tud shares 19-20% identity and 34-35% similarity with the human genes.
Moderate-scoring ortholog of human NANOS1, NANOS2, and NANOS3 (1 Drosophila to 3 human). Within a small region defined as the nanos RNA-binding domain, Dmel\nos shares 52-61% identity and 69-72% similarity with the human genes; beyond this region there is little detected homology.
Moderate-scoring ortholog of human DDX4 (1 Drosophila to 1 human). Dmel\vas shares 43% identity and 57% similarity with the human gene.
Low- to moderate-scoring ortholog of human PIWIL1, PIWIL3, PIWIL4, and PIWIL2 (3 Drosophila to 4 human). Dmel\piwi shares 31-36% identity and 52-56% similarity with the human genes.
Moderate-scoring ortholog of human PIWIL1, PIWIL3, PIWIL4, and PIWIL2 (3 Drosophila to 4 human). Dmel\aub shares 31-37% identity and 51-56% similarity with the human genes.
High-scoring ortholog of human TIMM50 (3 Drosophila to 1 human).
Moderate-scoring ortholog of human TOMM20 and TOMM20L (2 Drosophila to 2 human).