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Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin

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  • Aishwarya Iyer
  • Dylan Hennessey
  • Sandra O'Keefe
  • Jordan Patterson
  • Weiwei Wang
  • Gane Ka-Shu Wong
  • Robert Gniadecki
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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.

Original languageEnglish
JournalScientific Reports
Volume10
Issue number1
Pages (from-to)15483
ISSN2045-2322
DOIs
Publication statusPublished - 23 Sep 2020

    Research areas

  • Epidermis/metabolism, Genes, Neoplasm/genetics, Humans, Lymphoma/genetics, Mutation/genetics, Phylogeny, Skin/metabolism, Skin Neoplasms/genetics, T-Lymphocytes/metabolism, Tumor Microenvironment/genetics

ID: 61800564