TY - JOUR
T1 - Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas
AU - Daniels, Jay
AU - Doukas, Peter G.
AU - Escala, Maria E.Martinez
AU - Ringbloom, Kimberly G.
AU - Shih, David J.H.
AU - Yang, Jingyi
AU - Tegtmeyer, Kyle
AU - Park, Joonhee
AU - Thomas, Jane J.
AU - Selli, Mehmet E.
AU - Altunbulakli, Can
AU - Gowthaman, Ragul
AU - Mo, Samuel H.
AU - Jothishankar, Balaji
AU - Pease, David R.
AU - Pro, Barbara
AU - Abdulla, Farah R.
AU - Shea, Christopher
AU - Sahni, Nidhi
AU - Gru, Alejandro A.
AU - Pierce, Brian G.
AU - Louissaint, Abner
AU - Guitart, Joan
AU - Choi, Jaehyuk
N1 - Funding Information:
We thank the patients who contributed to this study. We thank the NIH Tetramer Core Facility for providing Human CD1d PBS 57-APC tetramer, the Northwestern Skin Disease Research Center (DNA/RNA Delivery Core), the Robert H. Lurie Comprehensive Cancer Center (Flow Cytometry Core), the Skin Biology and Diseases Resource-Based Center, and the Northwestern University Research Computing Services for their invaluable contribution for providing effective solutions for the storage and analysis of data. We thank Admera Health for performing next generation sequencing. This study was supported in part by the National Institutes of Health, National Cancer Institute (J.C., grant K08-CA191019-01A1), NIH Director’s New Innovator Award, (J.C., 1DP2AI136599-01), the American Cancer Society (J.C., grant ACS-IRG-15-173-21), the Skin Cancer Foundation Research Grant (J. C.), and the Leukemia Research Foundation New Investigator Grant (J.C.). This work was supported by the Doris Duke Charitable Foundation Clinical Scientist Development Award (Grant# 2016095), Doris Duke Research Data Sharing Award (Grant #2019107), and in part by the Damon Runyon Cancer Research Foundation (DRCRF# CI-84-16). J.D. was supported in part by NIH/NCI training grant T32 CA009560. This research was also supported in part by grants to N.S. (CPRIT Scholar in Cancer Research Grant RR160021; Alfred P. Sloan Research Fellowship FG-2018-10723), to B.P. (NIH R01 GM126299), and to B.J. (NIH NIDDK grant #T35DK062719-29). This research was supported in part by resources provided by the Northwestern University Skin Biology and Diseases Resource-based Center (P30 AR075049), Chicago, IL with support from the NIH/NIAMS. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the Northwestern University Skin Biology and Diseases Resource-based Center or the NIH/NIAMS.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-15572-7
DO - 10.1038/s41467-020-15572-7
M3 - Article
C2 - 32286303
AN - SCOPUS:85083545642
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1806
ER -