Grant: Project Grant

Cutaneous T-Cell Lymphoma (CTCL) is the most common lymphoma of the skin. Despite recent advances, this lymphoma remains difficult to diagnose (time to diagnosis ~6 years) because it mimics other common skin rashes such as eczema and psoriasis. It is also not possible to predict which patients with early stage CTCL will progress to advanced stages. Furthermore, advanced CTCL remains difficult to treat with a median survival of only 2-4 years. Hence, new diagnostic/prognostic markers and novel therapeutic targets are urgently needed to aid the medical management of this cancer. We showed that a number of programs that are usually only present in germline tissues (testis/ovaries) are abnormally re-expressed in CTCL. We are proposing to study how reactivation of these genes/programs (e.g., LINE-1 retrotransposition, cancer testis/meiosis regulatory genes) arises contributing to genomic instability, CTCL cancer development and progression. Since these programs are usually not expressed in healthy somatic tissues, their upregulation could be used as a diagnostic marker. Also, since these genes likely promote cancer progression, their expression in early stages may serve as a harbinger for an aggressive disease requiring systemic therapy. Finally, activity of several of these genes is likely central to cancer cell division/survival and, hence, targeting them may lead to novel therapies for CTCL patients. In the proposed grant we will study expression/activation patterns for these genes, their regulation and molecular function in CTCL, determine how they could be used as novel diagnostic/prognostic markers and exploited as therapeutic targets. This project will produce a reliable set of markers that will help shorten the time to diagnosis and help distinguish CTCL from other benign skin rashes; select prognostic markers that will identify early stage patients requiring aggressive therapies and define how these important genes/proteins could be targeted to treat CTCL.