The Neoantigen Landscape of Mycosis Fungoides

Sivanand, Arunima; Hennessey, Dylan; Iyer, Aishwarya; OʼKeefe, Sandra; Surmanowicz, Philip; Vaid, Gauravi; Xiao, Zixuan; Gniadecki, Robert

doi:10.3389/fimmu.2020.561234

Cited by 8 publications

(7 citation statements)

References 54 publications

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“…Genetic aberration involving cell cycle and proliferation, chromosomal instability, and DNA repair have been observed in MF/SS [ 28 ]. Those genes are involved in different pathways such as epigenetic and/or chromatin regulation, TCR and T-cell/ cytokine signalling, Jak/signal transducer and activator of transcription (STAT), and phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt) and NF-kB pathway, configuring that a complex mutational landascape may be related to MF/SS pathogenesis [ 27 , 29 , 30 ]. Also microenvironment changes from early to advanced CTCL phases have been proposed in the pathogenesis of MF and SS.…”

Section: Introductionmentioning

confidence: 99%

TOX Expression in Mycosis Fungoides and Sezary Syndrome

et al. 2022

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Mycosis fungoides (MF) and Sezary syndrome (SS) are the two most common type of cutaneous T-cell lymphoma (CTCL). Currently, no markers can be clearly related to prognosis or to differential diagnosis between early stages and inflammatory benign diseases (IBD). The thymocyte selection-associated high mobility group box factor (TOX), has been proposed as a possible marker in differential diagnosis between early CTCL stages and IBD. Recently TOX has been related to prognosis. We aimed to investigate whether TOX may be a diagnostic or prognostic marker. MF and SS biopsies between 2010 and 2020 were retrieved. New tissues slides were stained with an anti-TOX antibody, (Clone NAN448B). On each slide, 5 fields were examined at high magnification (400×), to evaluate the percentage of marker-positivity in a quantitative way. Thirty-six patients (12 females and 24 males) and 48 biopsies were collected. Nine patients had multiple biopsies. TOX expression in MF/SS cases showed an increase from early to advanced phases. TOX was not regarded as a prognostic marker due to the absence of significant changes by comparing early MF cases with reactive conditions. TOX statistical significance increased in patients alive with disease and in those dead of disease (p = 0.013 and = 0.0005, respectively) as compared with patients in complete remission. Our results show that TOX should be regarded more as a prognostic than a diagnostic marker.

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Section: Introductionmentioning

confidence: 99%

TOX Expression in Mycosis Fungoides and Sezary Syndrome

et al. 2022

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“…The same was previously seen on the mutational level: LSP resembled tumours and differed from the ESP. 17,76 This shows that stage progression is associated with global genomic and transcriptomic changes in all skin lesions, even though the tumour formation is present only in a discrete skin area. Thus, cancer cells in MF are likely to percolate through the skin, occasionally seeding new areas and the existing lesions, the latter case resembling tumour self-seeding or cell exchange between distant metastases (Figure 5b, c).…”

Section: Discussionmentioning

confidence: 96%

Transcriptomic changes during stage progression of mycosis fungoides

et al. 2021

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Summary 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 patients with MF develop skin tumours, a hallmark of progression to the advanced stage, which is associated with high mortality. The mechanisms involved in stage progression are poorly elucidated. Objectives We sought to address the hypothesis of MF cell trafficking between skin lesions by comparing transcriptomic profiles of skin samples in different clinical stages of MF. 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) as well as plaques and tumours from patients in late‐stage disease [late‐stage plaques (LSP, n = 10) and tumours (TMR, n = 15)]. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine pathway changes specific for different lesions which were linked to the recurrent somatic mutations overrepresented in MF tumours. Results The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt‐mTOR), T helper cell (Th)2/Th9 signalling [interleukin (IL)4, STAT3, STAT5, STAT6], meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, 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 haematogenous self‐seeding. Conclusions 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 may be caused by haematogenous cell percolation between discrete skin lesions.

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“…The same was previously seen on the mutational level: LSP resembled tumors and differed from the ESP. 17,68 This shows that stage progression is associated with global genomic and transcriptomic changes in all skin lesions, in spite of the fact that the tumor formation is only present in a discrete skin area. Thus, cancer cells in MF are likely to percolate through the skin, occasionally seeding new areas and the existing lesions, the latter case resembling tumor self-seeding or cell exchange between distant metastases (Figure 5B).…”

Section: Discussionmentioning

confidence: 96%

Transcriptomic Changes During Stage Progression of Mycosis Fungoides

Xiao

Hennessey

Iyer

et al. 2021

Preprint

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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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The Neoantigen Landscape of Mycosis Fungoides

Cited by 8 publications

References 54 publications

TOX Expression in Mycosis Fungoides and Sezary Syndrome

TOX Expression in Mycosis Fungoides and Sezary Syndrome

Transcriptomic changes during stage progression of mycosis fungoides

Transcriptomic Changes During Stage Progression of Mycosis Fungoides

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