Constitutional promoter methylation and risk of familial melanoma

Hyland, Paula L.; Burke, Laura; Pfeiffer, Ruth M.; Rotunno, Melissa; Sun, David; Patil, Prasad; Wu, Xiaolin; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.

doi:10.4161/epi.28151

Cited by 13 publications

(8 citation statements)

References 30 publications

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“…Since the array platform contains CDKN2A CpGs not specifically associated with p16, we investigated additional CDKN2A promoter CpGs by pyrosequencing. The melanoma patients exhibited low methylation levels for CDKN2A , similar to the pattern already reported for healthy individuals [ 23 ]. Our data in this Brazilian cohort of patients are in accordance with previous studies that described absence of CDKN2A epimutation in hereditary melanoma patients [ 20 , 21 ].…”

Section: Discussionsupporting

confidence: 83%

“…In addition to genetic mutations, early events of anomalous DNA methylation at specific loci (epimutations) can eventually result in cancer predisposition, as already reported for colorectal [ 16 , 17 ], gastric [ 18 ], and breast cancers [ 19 ]. Although melanoma epimutations have not been identified so far [ 20 , 21 ], abnormal methylation levels of TNF and TNFRSF10C genes have been associated with melanoma risk [ 22 , 23 ]. Moreover, somatic DNA methylation changes are crucial for skin melanoma progression [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients

Araújo

Pramio

Kashiwabara

et al. 2015

BioMed Research International

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In melanoma development, oncogenic process is mediated by genetic and epigenetic mutations, and few studies have so far explored the role of DNA methylation either as predisposition factor or biomarker. We tested patient samples for germline CDKN2A methylation status and found no evidence of inactivation by promoter hypermethylation. We have also investigated the association of clinical characteristics of samples with the DNA methylation pattern of twelve genes relevant for melanomagenesis. Five genes (BAP1, MGMT, MITF, PALB2, and POT1) presented statistical association between blood DNA methylation levels and either CDKN2A-mutation status, number of lesions, or Breslow thickness. In tumors, five genes (KIT, MGMT, MITF, TERT, and TNF) exhibited methylation levels significantly different between tumor groups including acral compared to nonacral melanomas and matched primary lesions and metastases. Our data pinpoint that the methylation level of eight melanoma-associated genes could potentially represent markers for this disease both in peripheral blood and in tumor samples.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients

Araújo

Pramio

Kashiwabara

et al. 2015

BioMed Research International

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“…We consider it possible, but unlikely that lower methylation levels of a single CpG site in the distal promoter of ROS1 would cause familial melanoma. Similar to the finding of TNFRSF10C hypomethylation in familial melanoma patients from the USA, which we could not detect in our patients, this finding might be analysed in a large number of melanoma families [17].…”

Section: Resultssupporting

confidence: 91%

“…A previous study analysed methylation of 14 cancerrelated genes in blood DNA from melanoma-prone family members. This analysis revealed no constitutional promoter hypermethylation, but reduced methylation of the TNFRSF10C promoter [17].…”

Section: Introductionmentioning

confidence: 80%

Genome-wide analysis of constitutional DNA methylation in familial melanoma

et al. 2020

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Background: Heritable epigenetic alterations have been proposed as an explanation for familial clustering of melanoma. Here we performed genome-wide DNA methylation analysis on affected family members not carrying pathogenic variants in established melanoma susceptibility genes, compared with healthy volunteers. Results: All melanoma susceptibility genes showed the absence of epimutations in familial melanoma patients, and no loss of imprinting was detected. Unbiased genome-wide DNA methylation analysis revealed significantly different levels of methylation in single CpG sites. The methylation level differences were small and did not affect reported tumour predisposition genes. Conclusion: Our results provide no support for heritable epimutations as a cause of familial melanoma.

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“…The methylation profile of the other genes that we have studied revealed generally hypomethylated or mildly hypomethylated clones with no significant difference between the untreated and cadmium-treated cells. The silencing of p16 INK4A and caspase 8 by cadmium in melanoma cells is of particular importance in light of the negligible role played by constitutional epimutations of CDKN2A (p16 INK4A and p14 ARF ) genes in melanoma families, whereby it was concluded that it is unlikely that they play a role in susceptibility to the disease in families without CDKN2A mutations [ 202 ]. These findings are coherent with those of others which aimed at identifying germline epimutations of genes that were found to be mutated in familial cutaneous malignant melanoma.…”

Section: Cadmium and Melanomamentioning

confidence: 99%

Epigenetic Effects of Cadmium in Cancer: Focus on Melanoma

Venza¹,

Visalli²,

Biondo³

et al. 2015

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Cadmium is a highly toxic heavy metal, which has a destroying impact on organs. Exposure to cadmium causes severe health problems to human beings due to its ubiquitous environmental presence and features of the pathologies associated with pro-longed exposure. Cadmium is a well-established carcinogen, although the underlying mechanisms have not been fully under-stood yet. Recently, there has been considerable interest in the impact of this environmental pollutant on the epigenome. Be-cause of the role of epigenetic alterations in regulating gene expression, there is a potential for the integration of cadmium-induced epigenetic alterations as critical elements in the cancer risk assessment process. Here, after a brief review of the ma-jor diseases related to cadmium exposure, we focus our interest on the carcinogenic potential of this heavy metal. Among the several proposed pathogenetic mechanisms, particular attention is given to epigenetic alterations, including changes in DNA methylation, histone modifications and non-coding RNA expression. We review evidence for a link between cadmium-induced epigenetic changes and cell transformation, with special emphasis on melanoma. DNA methylation, with reduced expression of key genes that regulate cell proliferation and apoptosis, has emerged as a possible cadmium-induced epigenetic mechanism in melanoma. A wider comprehension of mechanisms related to this common environmental contaminant would allow a better cancer risk evaluation.

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Constitutional promoter methylation and risk of familial melanoma

Cited by 13 publications

References 30 publications

DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients

DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients

Genome-wide analysis of constitutional DNA methylation in familial melanoma

Epigenetic Effects of Cadmium in Cancer: Focus on Melanoma

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