Prognostic Utility of CpG Island Hypermethylated Phenotype in Early-Stage Invasive Primary Melanomas

Bustos, Matías A.; Hoon, Dave S.B.

doi:10.1016/j.jid.2021.12.013

Cited by 2 publications

(1 citation statement)

References 9 publications

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“…Cancer development is associated with extensive changes in methylation levels of cytosines within 5'-cytosine-phosphate-guanine-3' dinucleotides (CpGs) [1]. Differential methylation plays an important role in initiation [2], progression [3][4][5], immune cell infiltration [6,7] and response to treatment [8,9] in many cancer types including cutaneous melanoma [10][11][12][13][14]. DNA methylation plays an important role in the regulation of gene expression [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Methylation of nonessential genes in cutaneous melanoma – Rule Out hypothesis

et al. 2023

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Differential methylation plays an important role in melanoma development and is associated with survival, progression and response to treatment. However, the mechanisms by which methylation promotes melanoma development are poorly understood. The traditional explanation of selective advantage provided by differential methylation postulates that hypermethylation of regulatory 5’-cytosine-phosphate-guanine-3’ dinucleotides (CpGs) downregulates the expression of tumor suppressor genes and therefore promotes tumorigenesis. We believe that other (not necessarily alternative) explanations of the selective advantages of methylation are also possible. Here, we hypothesize that melanoma cells use methylation to shut down transcription of nonessential genes – those not required for cell survival and proliferation. Suppression of nonessential genes allows tumor cells to be more efficient in terms of energy and resource usage, providing them with a selective advantage over the tumor cells that transcribe and subsequently translate genes they do not need. We named the hypothesis the Rule Out (RO) hypothesis. The RO hypothesis predicts higher methylation of CpGs located in regulatory regions (CpG islands) of nonessential genes. It also predicts the higher methylation of regulatory CpGs linked to nonessential genes in melanomas compared to nevi and lower expression of nonessential genes in malignant (derived from melanoma) versus normal (derived from nonaffected skin) melanocytes. The analyses conducted using in-house and publicly available data found that all predictions derived from the RO hypothesis hold, providing observational support for the hypothesis.

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Section: Introductionmentioning

confidence: 99%

Methylation of nonessential genes in cutaneous melanoma – Rule Out hypothesis

et al. 2023

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Epigenetics of Conjunctival Melanoma: Current Knowledge and Future Directions

Flick,

Demirci,

Demirci

2024

Cancers

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The purpose of this article is to provide a literature review of the epigenetic understanding of conjunctival melanoma (CM), with a primary focus on current gaps in knowledge and future directions in research. CM is a rare aggressive cancer that predominantly affects older adults. Local recurrences and distant metastases commonly occur in CM patients; however, their prediction and management remain challenging. Hence, there is currently an unmet need for useful biomarkers and more effective treatments to improve the clinical outcomes of these patients. Like other cancers, CM occurrence and prognosis are believed to be influenced by multiple genetic and epigenetic factors that contribute to tumor development/progression/recurrence/spread, immune evasion, and primary/acquired resistance to therapies. Epigenetic alterations may involve changes in chromatin conformation/accessibility, post-translational histone modifications or the use of histone variants, changes in DNA methylation, alterations in levels/functions of short (small) or long non-coding RNAs (ncRNAs), or RNA modifications. While recent years have witnessed a rapid increase in available epigenetic technologies and epigenetic modulation-based treatment options, which has enabled the development/implementation of various epi-drugs in the cancer field, the epigenetic understanding of CM remains limited due to a relatively small number of epigenetic studies published to date. These studies primarily investigated DNA methylation, ncRNA (e.g., miRNA or circRNA) expression, or RNA methylation. While these initial epigenetic investigations have revealed some potential biomarkers and/or therapeutic targets, they had various limitations, and their findings warrant replication in independent and larger studies/samples. In summary, an in-depth understanding of CM epigenetics remains largely incomplete but essential for advancing our molecular knowledge and improving clinical management/outcomes of this aggressive disease.

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Prognostic Utility of CpG Island Hypermethylated Phenotype in Early-Stage Invasive Primary Melanomas

Cited by 2 publications

References 9 publications

Methylation of nonessential genes in cutaneous melanoma – Rule Out hypothesis

Methylation of nonessential genes in cutaneous melanoma – Rule Out hypothesis

Epigenetics of Conjunctival Melanoma: Current Knowledge and Future Directions

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