期刊
SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41598-020-72459-9
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资金
- Canadian Dermatology Foundation [CDF RES0035718]
- University Hospital Foundation (University of Alberta)
- Danish Cancer Society (Kraeftens Bekaempelse) [R124-A7592 Rp12350]
- Department of Medicine, University of Alberta
- Bispebjerg Hospital (Copenhagen, Denmark)
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.
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