Transcriptional Profiling Use to Improve Personalized Diagnosis and Management of Cutaneous T-Cell Lymphoma (CTCL)

Cutaneous T-cell lymphoma (CTCL) can be a diagnostic challenge for clinicians and also follows an unpredictable disease course in which there are no prognostic markers currently available. Recently, transcriptional profiling of cancer cells has emerged as a valuable clinical tool for disease stratification into molecular subgroups with prognostic significance and treatment implications. Global gene expression analysis has been performed in CTCL, first via microarray then by next-generation sequencing, to characterize differential gene expression, define novel subgroups of disease, and generate prognostic models. In a thoroughly studied cohort of CTCL patients analyzed in this manner, three distinct clusters of diseases have been identified which are predictive of prognosis beyond the presenting clinical stage. In general, genes associated with inflammatory signaling and immune response are upregulated in progressive disease, consistent with the notion of malignant inflammation in a pro-tumorigenic microenvironment. Furthermore, over 200 genes with known association with CTCL pathogenesis have been individually tested by RT-PCR, revealing a panel of 17 genes that can distinguish CTCL from benign mimickers and also predict disease prognosis. External validation studies have corroborated these findings, and RNA sequencing methods have identified TOX, FYB, CD52, and CCR4 to be robust predictors of progression from early-stage disease. Ectopically expressed developmental and cancer/testis genes have also been identified and may represent novel therapeutic targets. Taken together, large-scale gene expression studies have laid the groundwork for the development of a personalized molecular approach toward improving the diagnosis and management of CTCL.