Transcriptomic Changes During Stage Progression of Mycosis Fungoides

Transcriptomic changes during stage progression of mycosis fungoides: from translational analyses to their potential clinical implications

British Journal of Dermatology ◽

10.1111/bjd.20895 ◽

2021 ◽

Author(s):

G. Dobos ◽

C. Assaf

Keyword(s):

Mycosis Fungoides ◽

Clinical Implications ◽

Stage Progression ◽

Transcriptomic Changes

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Transcriptomic Changes During Stage Progression of Mycosis Fungoides

10.1101/2021.04.20.440708 ◽

2021 ◽

Author(s):

Maggie Xiao ◽

Dylan Hennessey ◽

Aishwarya Iyer ◽

Sandra O'Keefe ◽

Frederick Zhang ◽

...

Keyword(s):

Mycosis Fungoides ◽

Late Stage ◽

Early Stage ◽

Skin Lesions ◽

Advanced Stage ◽

Stage Progression ◽

Whole Exome ◽

Stage Disease ◽

Skin Biopsies ◽

Transcriptomic Changes

Background: Mycosis fungoides (MF) is the most common cutaneous T cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ~25% of MF patients develop skin tumors, a hallmark of progression to the advanced stage and associated with high mortality. The mechanisms involved in stage progression are poorly elucidated. Methods: We performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n=12), and plaques and tumors from patients in late-stage disease (late-stage plaques, LSP, n=10, and tumors, TMR, n=15). Gene Ontology (GO) and KEGG analysis were used to determine pathway changes specific for different lesions which we linked to the recurrent somatic mutations overrepresented in MF tumors. Results: The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), Th2/Th9 signaling (IL4, STAT3, STAT5, STAT6), meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, and REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via hematogenous self-seeding. Conclusion: Stage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions are probably caused by hematogenous cell percolation between discrete skin lesions.

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Patterns of Gene Expression in Cutaneous T-Cell Lymphoma: Systematic Review of Transcriptomic Studies in Mycosis Fungoides

Cells ◽

10.3390/cells10061409 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1409

Author(s):

Melika Motamedi ◽

Maggie Z. X. Xiao ◽

Aishwarya Iyer ◽

Robert Gniadecki

Keyword(s):

Systematic Review ◽

Mycosis Fungoides ◽

Chromosomal Instability ◽

Cell Lymphoma ◽

Immune Checkpoints ◽

Cutaneous T Cell Lymphoma ◽

Risk Of Mortality ◽

Increased Risk ◽

Transcriptomic Changes ◽

Late Stages

Mycosis fungoides (MF) is the most prevalent type of skin lymphoma. In its early stages, it has a favorable prognosis. However, in its late stages, it is associated with an increased risk of mortality. This systematic review aimed to identify the transcriptomic changes involved in MF pathogenesis and progression. A literature search was conducted using the database PubMed, followed by the extraction of 2245 genes which were further filtered to 150 recurrent genes that appeared in two or more publications. Categorization of these genes identified activated pathways involved in pathways such as cell cycle and proliferation, chromosomal instability, and DNA repair. We identified 15 genes implicated in MF progression, which were involved in cell proliferation, immune checkpoints, resistance to apoptosis, and immune response. In highlighting the discrepancies in the way MF transcriptomic data is obtained, further research can focus on not only unifying their approach but also focus on the 150 pertinent genes identified in this review.

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