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

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TitleCellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas.
Publication TypeJournal Article
Year of Publication2020
AuthorsDaniels, J, Doukas, PG, Escala, MEMartinez, Ringbloom, KG, Shih, DJH, Yang, J, Tegtmeyer, K, Park, J, Thomas, JJ, Selli, ME, Altunbulakli, C, Gowthaman, R, Mo, SH, Jothishankar, B, Pease, DR, Pro, B, Abdulla, FR, Shea, C, Sahni, N, Gru, AA, Pierce, BG, Louissaint, A, Guitart, J, Choi, J
JournalNat Commun
Volume11
Issue1
Pagination1806
Date Published2020 Apr 14
ISSN2041-1723
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.

DOI10.1038/s41467-020-15572-7
Alternate JournalNat Commun
PubMed ID32286303
Grant ListT32 CA009560 / CA / NCI NIH HHS / United States
K08-CA191019-01A1 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
T35DK062719-29 / / U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) /
RR160021 / / Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) /
FG-2018-10723 / / Alfred P. Sloan Foundation /
R01 GM126299 / GM / NIGMS NIH HHS / United States
1DP2AI136599-01 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
ACS-IRG-15-173-21 / / American Cancer Society (American Cancer Society, Inc.) /
n/a / / Leukemia Research Foundation (LRF) /
DRCRF# CI-84-16 / / Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) /
DDCF# 2016095 / / Doris Duke Charitable Foundation (DDCF) /
n/a / / Skin Cancer Foundation /