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

Jay Daniels, Peter G. Doukas, Maria E. Martinez Escala, Kimberly G. Ringbloom, David J. H. Shih, Jingyi Yang, Kyle Tegtmeyer, Joonhee Park, Jane J. Thomas, Mehmet E. Selli, Can Altunbulakli, Ragul Gowthaman, Samuel H. Mo, Balaji Jothishankar, David R. Pease, Barbara Pro, Farah R. Abdulla, Christopher Shea, Nidhi Sahni, Alejandro A. Gru, Brian G. Pierce, Abner Louissaint (), Joan Guitart () and Jaehyuk Choi ()
Additional contact information
Jay Daniels: Northwestern University Feinberg School of Medicine
Peter G. Doukas: Northwestern University Feinberg School of Medicine
Maria E. Martinez Escala: Northwestern University Feinberg School of Medicine
Kimberly G. Ringbloom: Northwestern University Feinberg School of Medicine
David J. H. Shih: The University of Texas MD Anderson Cancer Center
Jingyi Yang: Northwestern University Feinberg School of Medicine
Kyle Tegtmeyer: Northwestern University Feinberg School of Medicine
Joonhee Park: Northwestern University Feinberg School of Medicine
Jane J. Thomas: Northwestern University Feinberg School of Medicine
Mehmet E. Selli: Northwestern University Feinberg School of Medicine
Can Altunbulakli: Northwestern University Feinberg School of Medicine
Ragul Gowthaman: University of Maryland Institute for Bioscience and Biotechnology Research
Samuel H. Mo: University of Illinois College of Medicine
Balaji Jothishankar: University of Chicago Pritzker School of Medicine
David R. Pease: Northwestern University Feinberg School of Medicine
Barbara Pro: Northwestern University Feinberg School of Medicine
Farah R. Abdulla: City of Hope Comprehensive Cancer Center
Christopher Shea: University of Chicago Pritzker School of Medicine
Nidhi Sahni: The University of Texas MD Anderson Cancer Center
Alejandro A. Gru: University of Virginia Health System
Brian G. Pierce: University of Maryland Institute for Bioscience and Biotechnology Research
Abner Louissaint: Massachusetts General Hospital
Joan Guitart: Northwestern University Feinberg School of Medicine
Jaehyuk Choi: Northwestern University Feinberg School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Primary cutaneous γδ 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 γδ lymphomas. We find that PCGDTLs are not uniformly derived from Vδ2 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 Vδ1 cells, the predominant γδ cell in the epidermis and dermis. In contrast, panniculitic lymphomas arise from Vδ2 cells, the predominant γδ T cell in the fat. We also show that TCR chain usage is non-random, suggesting common antigens for Vδ1 and Vδ2 lymphomas respectively. In addition, Vδ1 and Vδ2 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.

Date: 2020
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DOI: 10.1038/s41467-020-15572-7

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