Cutaneous T-cell lymphoma (CTCL) is a non-Hodgkin lymphoma characterized by malignant monoclonal T-lymphocytes that infiltrate the dermis, align within the basal layer and present in the dermis. Differential diagnosis of CTCL poses a challenge to clinicians due to its propensity to mimic benign dermatoses such as psoriasis and eczema by presenting with localized erythroderma, and red and itchy patches. Meiosis-specific cancer/testis (meiCT) antigens are a specialized group of genes expressed specifically in meiosis and epigenetically silenced in normal somatic cells. 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 patients and healthy controls using publicly available RNA Seq data. We validated our in solico analysis by examining the expression of 5 meiCT proteins in FFPE lesional samples from CTCL patients. Our results show significant differential gene expression of STAG3, SGO2, SYCP3 and DMC1 in a cohort of Sézary Syndrome patients when compared to healthy controls. Additionally, our study demonstrates 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 samples. Additionally, we discovered, through the use of the histone acetyltransferase inhibitor (HATi), anacardic acid, that meiCT genes are epigenetically regulated in CTCL and may also possess a level of post-transcriptional regulation at the protein level. Importantly, we have shown 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 and with further investigation may be an important diagnostic biomarker to differentiate CTCL from benign dermatoses. 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 skin conditions and will set a precedent to develop more targeted therapies for patients with this malignancy.

Expression of meiosis regulatory genes in cutaneous T-cell lymphoma.