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

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...

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Vydáno v:	Nature communications Ročník 11; číslo 1; s. 1806 - 14
Hlavní autoři:	Daniels, Jay, Doukas, Peter G., Escala, Maria E. Martinez, Ringbloom, Kimberly G., Shih, David J. H., Yang, Jingyi, Tegtmeyer, Kyle, Park, Joonhee, Thomas, Jane J., Selli, Mehmet E., Altunbulakli, Can, Gowthaman, Ragul, Mo, Samuel H., Jothishankar, Balaji, Pease, David R., Pro, Barbara, Abdulla, Farah R., Shea, Christopher, Sahni, Nidhi, Gru, Alejandro A., Pierce, Brian G., Louissaint, Abner, Guitart, Joan, Choi, Jaehyuk
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 14.04.2020 Nature Publishing Group Nature Portfolio
Témata:	13/31 45/23 45/91 631/250/1619/554/2509 692/4028/67/69 Amino Acid Sequence Antigens Antigens, CD1d - metabolism Chromatin Chromatin Assembly and Disassembly Deoxyribonucleic acid Dermis DNA DNA sequencing Epidermis Epitopes - immunology Genome, Human Genomes HEK293 Cells Humanities and Social Sciences Humans Lymph Nodes - pathology Lymphocytes Lymphocytes T Lymphoma Lymphoma, T-Cell, Cutaneous - genetics Lymphoma, T-Cell, Cutaneous - pathology MAP kinase Models, Biological multidisciplinary Mutation Mutation - genetics Myc protein Ontogeny Phenotype Principal Component Analysis Receptors Receptors, Antigen, T-Cell, gamma-delta - metabolism Ribonucleic acid RNA Science Science (multidisciplinary) Signal Transduction Skin - pathology Skin Neoplasms - genetics Skin Neoplasms - pathology T cell receptors T-cell lymphoma Transcription, Genetic Transcriptome - genetics
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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. Cutaneous gamma-delta T cell lymphomas are rare but aggressive cancers. Here, by DNA, RNA and T cell receptor sequencing, the authors elucidate the molecular ontogeny by revising the cell of origin and identifying potentially targetable mutations.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-15572-7