Lessons learned from gene expression profiling of cutaneous T-cell lymphoma

Summary Gene expression studies of cutaneous T‐cell lymphoma (CTCL) span a decade, yet the pathogenesis is poorly understood and diagnosis remains a challenge. This review examines the varied approaches to gene expression analysis of CTCL, with emphasis on cell populations, control selection and expression data collection. Despite discordant results, several dysregulated genes have been identified across multiple studies, including PLS3, KIR3DL2, TWIST1 and STAT4. Here, we provide an overview of the most consistently expressed genes across different studies and bring them together through common pathways biologically relevant to CTCL. Four pathways – evasion of activation‐induced cell death, T helper 2 lymphocyte differentiation, transforming growth factor‐β receptor expression, and tumour necrosis factor receptor ligands – appear to encompass the most frequently affected genes, hypothetically providing insight into the disease pathogenesis. What's already known about this topic? Gene expression in cutaneous T‐cell lymphoma (CTCL) has been explored in a variety of diverse studies. Not surprisingly, considering the heterogeneous study designs, the results have also been discordant. What does this study add? We reconcile the differences in approaches to gene expression profiling and integrate them in a state‐of‐the‐art report. We summarize the most consistently expressed genes across different studies, and bring them together through common biologically relevant pathway analysis. We hypothesize how these commonly found abnormalities may be relevant to disease pathogenesis and provide a springboard for future genetic studies in CTCL.