New Frontiers in Melanoma Epigenetics—The More We Know, the More We Don’t Know

Nguyen, Marzena; Dobosz, Paula

doi:10.3390/epigenomes1010003

Cited by 6 publications

(2 citation statements)

References 164 publications

(198 reference statements)

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“…2 ). It functions as an off-switch, keeping T cells from launching an attack (Snyder 2016 ; Nguyen and Dobosz 2017 ; Gopalakrishnan et al 2018 ; Ishida 2020 ; Patsoukis et al 2020 ). To date, two ligands of PD-1 molecules have been discovered: PD-L1 and PD-L2.…”

Section: Overview Of the Immune Checkpoint Genes Regulation In Cancermentioning

confidence: 99%

Transcriptional and post-transcriptional regulation of checkpoint genes on the tumour side of the immunological synapse

Dobosz

Stempor²,

Moreno

et al. 2022

Heredity

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Cancer is a disease of the genome, therefore, its development has a clear Mendelian component, demonstrated by well-studied genes such as BRCA1 and BRCA2 in breast cancer risk. However, it is known that a single genetic variant is not enough for cancer to develop leading to the theory of multistage carcinogenesis. In many cases, it is a sequence of events, acquired somatic mutations, or simply polygenic components with strong epigenetic effects, such as in the case of brain tumours. The expression of many genes is the product of the complex interplay between several factors, including the organism’s genotype (in most cases Mendelian-inherited), genetic instability, epigenetic factors (non-Mendelian-inherited) as well as the immune response of the host, to name just a few. In recent years the importance of the immune system has been elevated, especially in the light of the immune checkpoint genes discovery and the subsequent development of their inhibitors. As the expression of these genes normally suppresses self-immunoreactivity, their expression by tumour cells prevents the elimination of the tumour by the immune system. These discoveries led to the rapid growth of the field of immuno-oncology that offers new possibilities of long-lasting and effective treatment options. Here we discuss the recent advances in the understanding of the key mechanisms controlling the expression of immune checkpoint genes in tumour cells.

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Section: Overview Of the Immune Checkpoint Genes Regulation In Cancermentioning

confidence: 99%

Transcriptional and post-transcriptional regulation of checkpoint genes on the tumour side of the immunological synapse

Dobosz

Stempor²,

Moreno

et al. 2022

Heredity

Self Cite

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“…Each cancer is bringing the signature of general hallmarks but also specific features. Next Generation Sequencing protocols and their ad hoc methodological pipelines have clearly indicated that a variety of molecular landscapes and profiles (expressional and mutational) exist, with melanoma as an example [2]. Additionally, the centrality of large-scale transcriptome studies and mutational approaches targeted to capture non-coding RNA evidences boosted the promised impact of epigenetic features [3].…”

Section: Introductionmentioning

confidence: 99%

Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures

et al. 2018

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BackgroundIn melanoma, like in other cancers, both genetic alterations and epigenetic underlie the metastatic process. These effects are usually measured by changes in both methylome and transcriptome profiles, whose cross-correlation remains uncertain. We aimed to assess at systems scale the significance of epigenetic treatment in melanoma cells with different metastatic potential.Methods and findingsTreatment by DAC demethylation with 5-Aza-2’-deoxycytidine of two melanoma cell lines endowed with different metastatic potential, SKMEL-2 and HS294T, was performed and high-throughput coupled RNA-Seq and RRBS-Seq experiments delivered differential profiles (DiP) of both transcriptomes and methylomes. Methylation levels measured at both TSS and gene body were studied to inspect correlated patterns with wide-spectrum transcript abundance levels quantified in both protein coding and non-coding RNA (ncRNA) regions. The DiP were then mapped onto standard bio-annotation sources (pathways, biological processes) and network configurations were obtained. The prioritized associations for target identification purposes were expected to elucidate the reprogramming dynamics induced by the epigenetic therapy. The interactomic connectivity maps of each cell line were formed to support the analysis of epigenetically re-activated genes. i.e. those supposedly silenced by melanoma. In particular, modular protein interaction networks (PIN) were used, evidencing a limited number of shared annotations, with an example being MAPK13 (cascade of cellular responses evoked by extracellular stimuli). This gene is also a target associated to the PANDAR ncRNA, therapeutically relevant because of its aberrant expression observed in various cancers. Overall, the non-metastatic SKMEL-2 map reveals post-treatment re-activation of a richer pathway landscape, involving cadherins and integrins as signatures of cell adhesion and proliferation. Relatively more lncRNAs were also annotated, indicating more complex regulation patterns in view of target identification. Finally, the antigen maps matched to DiP display other differential signatures with respect to the metastatic potential of the cell lines. In particular, as demethylated melanomas show connected targets that grow with the increased metastatic potential, also the potential target actionability seems to depend to some degree on the metastatic state. However, caution is required when assessing the direct influence of re-activated genes over the identified targets. In light of the stronger treatment effects observed in non-metastatic conditions, some limitations likely refer to in silico data integration tools and resources available for the analysis of tumor antigens.ConclusionDemethylation treatment strongly affects early melanoma progression by re-activating many genes. This evidence suggests that the efficacy of this type of therapeutic intervention is potentially high at the pre-metastatic stages. The biomarkers that can be assessed through antigens seem informative depending on the metastati...

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Epigenomic Markers in Dermato-oncology Immune Landscape

Constantin

Neagu

2023

Interdisciplinary Cancer Research

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New Frontiers in Melanoma Epigenetics—The More We Know, the More We Don’t Know

Cited by 6 publications

References 164 publications

Transcriptional and post-transcriptional regulation of checkpoint genes on the tumour side of the immunological synapse

Transcriptional and post-transcriptional regulation of checkpoint genes on the tumour side of the immunological synapse

Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures

Epigenomic Markers in Dermato-oncology Immune Landscape

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