Multiomic Study of Cutaneous T-Cell Lymphoma Reveals Single Cell Clonal Evolution in Progression and Therapy Resistance [bulk RNA-seq]

Multi-omics technologies offer the potential to provide uniquely precise views of disease progression and response to therapy. We present here a comprehensive multi-omics view of CTCL clonal evolution, incorporating exome, whole genome, epigenome, bulk-, single cell (sc) VDJ-, and scRNA- sequencing of 114 clinically annotated serial skin, peripheral blood, and lymph node samples from 35 CTCL patients.

We leveraged this extensive dataset to define the molecular underpinnings of CTCL progression in individual patients at single cell resolution with the goal of identifying clinically useful biomarkers and therapeutic targets. Our studies identified a large number of recurrent progression-associated clonal genomic alterations; we highlight mutation of CCR4, PI3K signaling, and PD-1 checkpoint pathways as evasion tactics deployed by malignant T cells.