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Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin
Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Lesions of MF are formed by hematogenous seeding the skin with polyclonal (clonotypically diverse) neoplastic T-cells which accumulate numerous mutations and display a high degree of mutational, intratumoral heterogeneity (ITH). A...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511331/ https://www.ncbi.nlm.nih.gov/pubmed/32968137 http://dx.doi.org/10.1038/s41598-020-72459-9 |
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author | Iyer, Aishwarya Hennessey, Dylan O’Keefe, Sandra Patterson, Jordan Wang, Weiwei Wong, Gane Ka-Shu Gniadecki, Robert |
author_facet | Iyer, Aishwarya Hennessey, Dylan O’Keefe, Sandra Patterson, Jordan Wang, Weiwei Wong, Gane Ka-Shu Gniadecki, Robert |
author_sort | Iyer, Aishwarya |
collection | PubMed |
description | Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Lesions of MF are formed by hematogenous seeding the skin with polyclonal (clonotypically diverse) neoplastic T-cells which accumulate numerous mutations and display a high degree of mutational, intratumoral heterogeneity (ITH). A characteristic but poorly studied feature of MF is epidermotropism, the tendency to infiltrate skin epithelial layer (epidermis) in addition to the vascularized dermis. By sequencing the exomes of the microdissected clusters of lymphoma cells from the epidermis and the dermis, we found that those microenvironments comprised different malignant clonotypes. Subclonal structure witnessed the independent mutational evolution in the epidermis and dermis. Thus, the epidermal involvement in MF could not be explained by gradual infiltration from the dermis but was caused by a separate seeding process followed by a quasi-neutral, branched evolution. In conclusion, tissue microenvironments shape the subclonal architecture in MF leading to “ecological heterogeneity” which contributes to the total ITH. Since ITH adversely affects cancer prognosis, targeting the microenvironment may present therapeutic opportunities in MF and other cancers. |
format | Online Article Text |
id | pubmed-7511331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75113312020-09-24 Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin Iyer, Aishwarya Hennessey, Dylan O’Keefe, Sandra Patterson, Jordan Wang, Weiwei Wong, Gane Ka-Shu Gniadecki, Robert Sci Rep Article Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Lesions of MF are formed by hematogenous seeding the skin with polyclonal (clonotypically diverse) neoplastic T-cells which accumulate numerous mutations and display a high degree of mutational, intratumoral heterogeneity (ITH). A characteristic but poorly studied feature of MF is epidermotropism, the tendency to infiltrate skin epithelial layer (epidermis) in addition to the vascularized dermis. By sequencing the exomes of the microdissected clusters of lymphoma cells from the epidermis and the dermis, we found that those microenvironments comprised different malignant clonotypes. Subclonal structure witnessed the independent mutational evolution in the epidermis and dermis. Thus, the epidermal involvement in MF could not be explained by gradual infiltration from the dermis but was caused by a separate seeding process followed by a quasi-neutral, branched evolution. In conclusion, tissue microenvironments shape the subclonal architecture in MF leading to “ecological heterogeneity” which contributes to the total ITH. Since ITH adversely affects cancer prognosis, targeting the microenvironment may present therapeutic opportunities in MF and other cancers. Nature Publishing Group UK 2020-09-23 /pmc/articles/PMC7511331/ /pubmed/32968137 http://dx.doi.org/10.1038/s41598-020-72459-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Iyer, Aishwarya Hennessey, Dylan O’Keefe, Sandra Patterson, Jordan Wang, Weiwei Wong, Gane Ka-Shu Gniadecki, Robert Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin |
title | Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin |
title_full | Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin |
title_fullStr | Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin |
title_full_unstemmed | Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin |
title_short | Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin |
title_sort | independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511331/ https://www.ncbi.nlm.nih.gov/pubmed/32968137 http://dx.doi.org/10.1038/s41598-020-72459-9 |
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