Molnar, CristinaHeinen, Jan PeterReina, JoséLlamazares, SaludPalumbo, EmilioPollarolo, GiuliaGonzález, Cayetano2024-07-102024-07-102024Molnar C, Heinen JP, Reina J, Llamazares S, Palumbo E, Pollarolo G, et al. TrxT and dhd are dispensable for Drosophila brain development but essential for l(3)mbt brain tumour growth. EMBO Rep. 2024 Jul;25(7):2842-60. DOI: 10.1038/s44319-024-00154-11469-221Xhttp://hdl.handle.net/10230/60716Expression of the Drosophila cancer-germline (CG), X-linked, head-to-head gene pair TrxT and dhd is normally germline-specific but becomes upregulated in brain tumours caused by mutation in l(3)mbt. Here, we show that TrxT and dhd play a major synergistic role in the emergence of l(3)mbt tumour-linked transcriptomic signatures and tumour development, which is remarkable, taking into account that these two genes are never expressed together under normal conditions. We also show that TrxT, but not dhd, is crucial for the growth of l(3)mbt allografts, hence suggesting that the initial stages of tumour development and long-term tumour growth may depend on different molecular pathways. In humans, head-to-head inverted gene pairs are abundant among CG genes that map to the X chromosome. Our results identify a first example of an X-linked, head-to-head CG gene pair in Drosophila, underpinning the potential of such CG genes, dispensable for normal development and homoeostasis of somatic tissue, as targets to curtail malignant growth with minimal impact on overall health.application/pdfeng© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associatinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s44319-024-00154-1Cancer-Germline GenesCancer-Testis GenesMalignant GrowthTumoursinfo:eu-repo/semantics/openAccess