Gametocyte Specific Factor 1 (GTSF1) ectopic expression in Cutaneous T-Cell Lymphoma (CTCL) patients has been shown to be associated with a worse prognosis. The objective of the study is to pinpoint the role of GTSF1 on carcinogenesis and elucidate how its ectopic expression is modifying patient outcome. GTSF1, a germline-cell specific gene, is an important element of the piRNA pathway. During germ-cell development, GTSF1 partners with the PIWI proteins to process small RNA molecules and identify active retrotransposons on the genome, recruiting the DNA methylation machinery to those sites. In cancer, hypomethylation of repetitive sequences and the subsequent activation of retrotransposons, leads to insertional mutagenesis and genomic instability. Data attained from The Cancer Genome Atlas (TCGA) was analyzed using a Bayesian Analysis and Markov Chain Monte Carlo Method to investigate expression levels of GTSF1 across 33 cancer types. To address the role of GTSF1, we performed shRNA mediated knockdown in CTCL cell lines. We employed several methodologies, such as qRT-PCR, Western Blot, immunofluorescence and a specialized retrotransposition assay, to evaluate the impact of GTSF1 on cell biology, retrotransposons, and genomic instability. Analysis from the TCGA data confirmed high levels of mRNA in lymphomas and leukemias. Western blot screening for the presence of additional piRNA pathway elements suggests that this pathway is not active in CTCL cell lines. Furthermore, knockdown of GTSF1 expression does not seem to affect retrotransposon protein expression and function. However, preliminary data does suggest that GTSF1 influences cell proliferation in lymphomas. In conclusion, preliminary data points to a previously unreported role of GTSF1 on cell biology. The aberrant expression of this gene poses an excellent clinical opportunity for targeted therapy development. Its germline cell restricted expression will potentially result in less side effects than current available therapies.

ESDR285 - Investigating the role of the ectopic expression of Gametocyte Specific Factor 1 in Cutaneous T-Cell Lymphomas

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING