Epigenetic signatures in cancer: proper controls, current challenges and the potential for clinical translation

Mancarella, Daniela; Plass, Christoph

doi:10.1186/s13073-021-00837-7

Cited by 64 publications

(30 citation statements)

References 105 publications

(101 reference statements)

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“…Cells of origin questions also persist for human MCC cell lines [ 80 ]. DNA methylation data can be used to identify the cell of origin [ 81 ], therefore, we took advantage of specific DNA methylation profiles based on tissue, cell, or cancer type to analyze the cell of origin for human MCC13 and MS-1 MCC cell lines. We compared MCC13 and MS-1 DNA methylation patterns with our patient MCC samples (Fig.…”

Section: Resultsmentioning

confidence: 99%

Characterizing DNA methylation signatures and their potential functional roles in Merkel cell carcinoma

Gujar

Mehta

et al. 2021

Genome Med

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Background Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with limited treatment possibilities. Merkel cell tumors display with neuroendocrine features and Merkel cell polyomavirus (MCPyV) infection in the majority (80%) of patients. Although loss of histone H3 lysine 27 trimethylation (H3K27me3) has been shown during MCC tumorigenesis, epigenetic dysregulation has largely been overlooked. Methods We conducted global DNA methylation profiling of clinically annotated MCC primary tumors, metastatic skin tumors, metastatic lymph node tumors, paired normal tissues, and two human MCC cell lines using the Illumina Infinium EPIC DNA methylation BeadArray platform. Results Significant differential DNA methylation patterns across the genome are revealed between the four tissue types, as well as based on MCPyV status. Furthermore, 964 genes directly regulated by promoter or gene body DNA methylation were identified with high enrichment in neuro-related pathways. Finally, our findings suggest that loss of H3K27me3 occupancy in MCC is attributed to KDM6B and EZHIP overexpression as a consequence of promoter DNA hypomethylation. Conclusions We have demonstrated specific DNA methylation patterns for primary MCC tumors, metastatic MCCs, and adjacent-normal tissues. We have also identified DNA methylation markers that not only show potential diagnostic or prognostic utility in MCC management, but also correlate with MCC tumorigenesis, MCPyV expression, neuroendocrine features, and H3K27me3 status. The identification of DNA methylation alterations in MCC supports the need for further studies to understand the clinical implications of epigenetic dysregulation and potential therapeutic targets in MCC.

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Section: Resultsmentioning

confidence: 99%

Characterizing DNA methylation signatures and their potential functional roles in Merkel cell carcinoma

Gujar

Mehta

et al. 2021

Genome Med

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“…Peculiarities such as the rapid kinetics and the transient nature of refractory phenotypes suggest the existence of an epigenetic basis for drug resistance in CM, pointing out that epigenetic regulation is a fundamental feature of tumor development and adaptation to therapy [ 157 ]. Accordingly, epigenetic alterations are currently being investigated as potential biomarkers and are being envisioned as promising therapeutic targets for CM clinical management [ 284 ].…”

Section: Discussionmentioning

confidence: 99%

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Dobre

Constantin

Costache

et al. 2021

JPM

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Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease.

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“…By determining these histone modifications, different chromatin states of region can be defined[ 107 ]. Histone modifications can be subjected to tightening or loose packaging under pathological conditions, including, cancer[ 108 , 109 ]. Histones are modified by specific enzymes.…”

Section: Epigenetic Regulation Of Cscs and Cancer Cellsmentioning

confidence: 99%

Epigenetic regulation of autophagy: A key modification in cancer cells and cancer stem cells

Mandhair¹,

Novak²,

Radpour³

2021

WJSC

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Aberrant epigenetic alterations play a decisive role in cancer initiation and propagation via the regulation of key tumor suppressor genes and oncogenes or by modulation of essential signaling pathways. Autophagy is a highly regulated mechanism required for the recycling and degradation of surplus and damaged cytoplasmic constituents in a lysosome dependent manner. In cancer, autophagy has a divergent role. For instance, autophagy elicits tumor promoting functions by facilitating metabolic adaption and plasticity in cancer stem cells (CSCs) and cancer cells. Moreover, autophagy exerts pro-survival mechanisms to these cancerous cells by influencing survival, dormancy, immunosurveillance, invasion, metastasis, and resistance to anti-cancer therapies. In addition, recent studies have demonstrated that various tumor suppressor genes and oncogenes involved in autophagy, are tightly regulated via different epigenetic modifications, such as DNA methylation, histone modifications and non-coding RNAs. The impact of epigenetic regulation of autophagy in cancer cells and CSCs is not well-understood. Therefore, uncovering the complex mechanism of epigenetic regulation of autophagy provides an opportunity to improve and discover novel cancer therapeutics. Subsequently, this would aid in improving clinical outcome for cancer patients. In this review, we provide a comprehensive overview of the existing knowledge available on epigenetic regulation of autophagy and its importance in the maintenance and homeostasis of CSCs and cancer cells.

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Epigenetic signatures in cancer: proper controls, current challenges and the potential for clinical translation

Cited by 64 publications

References 105 publications

Characterizing DNA methylation signatures and their potential functional roles in Merkel cell carcinoma

Characterizing DNA methylation signatures and their potential functional roles in Merkel cell carcinoma

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Epigenetic regulation of autophagy: A key modification in cancer cells and cancer stem cells

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