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- W2971822016 abstract "Cutaneous T-cell lymphoma (CTCL) is a non-Hodgkin lymphoma characterized by infiltrating malignant monoclonal T-lymphocytes. Differential diagnosis of CTCL poses a challenge to clinicians due to its propensity to mimic benign dermatoses such as psoriasis and eczema. Meiosis-specific cancer/testis (meiCT) antigens are a specialized group of genes expressed specifically in meiosis and epigenetically silenced in normal somatic cells, however recent research has demonstrated that a number of meiosis genes are ectopically upregulated in cancers, including CTCL. In this study we analyzed the transcriptional expression of meiCT genes in Sézary Syndrome (SS) patients and healthy controls using publicly available RNA Seq data. Our results show significant differential gene expression of STAG3, SGO2, SYCP3 and DMC1 in a cohort of SS patients when compared to healthy controls. Additionally, we demonstrated the heterogenous expression of meiCT genes involved in initiation (STRA8), sister chromatin cohesion (STAG3, SGO2), homologous chromosome synapsis (SYCP3) and homologous recombination (DMC1) in atypical lymphocytes in FFPE biopsy samples isolated from CTCL patients. Furthermore, CTCL cell line treatment with the histone acetyltransferase inhibitor, anacardic acid, demonstrated that meiCT genes are epigenetically regulated in CTCL and may also possess a level of post-transcriptional regulation at the protein level. Lastly, we show that epigenetic silencing of meiCT genes coincides with a reduction in double strand breaks as shown by a decrease in gamma-H2AX staining in the PB2B cell line. We conclude that the ectopic expression of meiCT genes are involved in increased genomic instability in CTCL. The ectopic expression of meiCT genes together with investigations into the functional mechanisms of cancer meiomitosis will help provide a foundation to develop novel diagnostic tests to distinguish CTCL from benign dermatoses and will set a precedent to develop more targeted therapies for patients with this malignancy." @default.
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- W2971822016 date "2019-09-01" @default.
- W2971822016 modified "2023-09-27" @default.
- W2971822016 title "478 Expression of meiosis regulatory genes in cutaneous T-cell lymphoma" @default.
- W2971822016 doi "https://doi.org/10.1016/j.jid.2019.07.528" @default.
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