Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas.

ABSTRACT: Primary cutaneous ?? T cell lymphomas (PCGDTLs) represent a heterogeneous group of uncommon but aggressive cancers. Herein, we perform genome-wide DNA, RNA, and T cell receptor (TCR) sequencing on 29 cutaneous ?? lymphomas. We find that PCGDTLs are not uniformly derived from V?2 cells. Instead, the cell-of-origin depends on the tissue compartment from which the lymphomas are derived. Lymphomas arising from the outer layer of skin are derived from V?1 cells, the predominant ?? cell in the epidermis and dermis. In contrast, panniculitic lymphomas arise from V?2 cells, the predominant ?? T cell in the fat. We also show that TCR chain usage is non-random, suggesting common antigens for V?1 and V?2 lymphomas respectively. In addition, V?1 and V?2 PCGDTLs harbor similar genomic landscapes with potentially targetable oncogenic mutations in the JAK/STAT, MAPK, MYC, and chromatin modification pathways. Collectively, these findings suggest a paradigm for classifying, staging, and treating these diseases.

SUBMITTER: Daniels J 

PROVIDER: S-EPMC7156460 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature