<i>MC1R</i> CpG island regulates <i>MC1R</i> expression and is methylated in a subset of melanoma tumours

Budden, Timothy

doi:10.1111/pcmr.12739

Cited by 7 publications

(9 citation statements)

References 22 publications

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“…Another study by Budden and Bowden described the regulation of MC1R expression by a CpG island overlapping a potential enhancer in the MC1R gene [26]. These authors found that this CpG island is unmethylated in melanocytes but highly methylated in other skin cell types.…”

Section: Discussionmentioning

confidence: 99%

“…Further analysis indicated that differential methylation of the CpG island in tumours mainly affected the expression of MC1R, and less so of TUBB3. Budden and Bowden also reported that there was weak evidence of increasing CpG island methylation levels with increasing numbers of red hair colour alleles (R) in melanoma tumours from The Cancer Genome Atlas (TCGA) dataset [26].…”

Section: Discussionmentioning

confidence: 99%

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Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer

Bonilla

Bertoni

Min

et al. 2020

Preprint

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BackgroundIncidence rates for melanoma and non-melanoma skin cancer (NMSC), which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), have been steadily increasing in all populations. Populations of European ancestry exhibit the highest rates and therefore, have been widely studied. Pigmentation characteristics are well-known risk factors for skin cancer, particularly fair skin, red hair, blue eyes and the inability to tan. Polymorphisms in established pigmentation-related genes have been associated with these traits and with an increased risk of malignancy. However, the functional relationship between genetic variation and disease is still unclear, with the exception of red hair colour variants in the melanocortin 1 receptor (MC1R) gene. ObjectivesThe aim of this study was to explore the possibility that non-coding pigmentation SNPs are associated with pigmentary traits and skin cancer via DNA methylation (DNAm). Methods and ResultsUsing a meta-GWAS of whole blood DNAm from 36 European cohorts (N=27,750; the Genetics of DNA Methylation Consortium, GoDMC), we found that 19 out of 27 pigmentation-associated SNPs distributed within 10 genes (ASIP, BNC2, IRF4, HERC2, MC1R, OCA2, SLC24A4, SLC24A5, SLC45A2, TYR) were associated with 391 DNAm sites across 30 genomic regions. We selected 25 DNAm sites for further analysis.We examined the effect of the chosen DNAm sites on pigmentation traits, sun exposure phenotypes, and skin cancer, and on gene expression in whole blood. We found an association of decreased DNAm at cg07402062 with red hair in the Avon Longitudinal Study of Parents and Children (ALSPAC), and a strong positive association of DNAm at this and correlated sites with higher expression of SPIRE2. Additionally, we investigated the association of gene expression in skin with pigmentation traits and skin cancer. The expression of ASIP, FAM83C, NCOA6, CDK10, and EXOC2 was associated with hair colour, whilst that of ASIP and CDK10 also had an effect on melanoma and BCC. ConclusionsOur results indicate that DNAm and expression of genes in the 16q24.3 and 20q11.22 regions, deserve to be further investigated as potential mediators of the relationship between genetic variants, pigmentation/sun exposure phenotypes, and some types of skin cancer.We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer

Bonilla

Bertoni

Min

et al. 2020

Preprint

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“…The correlation between MC1R and melanoma has been studied extensively, but the value of MC1R in the prognosis or therapeutic potential of CRC has been investigated to a lesser extent [22,23]. Studies have recently shown that MC1R participates in the occurrence and development of CRC [24].…”

Section: Discussionmentioning

confidence: 99%

MC1R Is a Prognostic Marker and Its Expression Is Correlated with MSI in Colorectal Cancer

Peng

Chang

et al. 2021

CIMB

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Melanocortin 1 receptor (MC1R) is thought to be a marker of poor prognosis and a potential target for the treatment of melanoma. Studies have found that MC1R promotes several tumor behaviors, including cell proliferation and differentiation, pigment formation, and genome damage repair. Some single-nucleotide polymorphisms (SNPs) of MC1R are involved in the occurrence and development of melanoma. A few studies have reported a relationship between MC1R and colorectal cancer (CRC). In this research, our objective was to examine MC1R expression and MC1R SNPs and investigate their correlation with the clinicopathological features of human CRC tissues. We evaluated MC1R mRNA expression by performing bioinformatic analyses on human CRC expression datasets. We used Western blotting and RT-qPCR to compare MC1R expression in CRC tissues with that in normal tissues, and MC1R SNPs in CRC tissues were detected by PCR-direct sequencing (DS). The expression of MC1R was significantly decreased in CRC tissues compared with normal tissue, and its expression was negatively associated with P53 expression, MLH1 expression, and PMS2 expression, and high MC1R expression was significantly associated with microsatellite instability (MSI). MC1R SNPs were also associated with the clinicopathological characteristics of CRC; for example, the rs2228479 locus genotype was correlated with Ki67 status, and the rs885479 locus genotype was correlated with age and T stage. In conclusion, MC1R plays a crucial role in the progression of CRC and may be a marker of poor prognosis in CRC.

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“…Epigenetic factors such as DNA-methylation chromatin-remodeling events, as well as gene regulation through non-coding RNAs play an important role in the pathogenesis of skin cancers [ 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 ]. Interestingly, epigenetic regulation of MC1R expression in melanoma has been recently investigated [ 209 ]. A methylated CpG-island (CGI) has been identified on a MC1R region, proposed as a MC1R enhancer.…”

Section: Epigenetic Regulation Of Mc1rmentioning

confidence: 99%

“…This CGI has been shown to control MC1R expression, with a slight trend of increased methylation in melanomas showing homozygous RHC MC1R , as compared to WT and heterozygous tumors. Interestingly, unmethylated tumors had a significantly worse prognosis compared to methylated tumors, although the prognostic effect of MC1R CGI methylation has not been fully elucidated [ 209 ].…”

Section: Epigenetic Regulation Of Mc1rmentioning

confidence: 99%

Behind the Scene: Exploiting MC1R in Skin Cancer Risk and Prevention

Manganelli

Guida

Ferretta

et al. 2021

Genes

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Melanoma and non-melanoma skin cancers (NMSCs) are the most frequent cancers of the skin in white populations. An increased risk in the development of skin cancers has been associated with the combination of several environmental factors (i.e., ultraviolet exposure) and genetic background, including melanocortin-1 receptor (MC1R) status. In the last few years, advances in the diagnosis of skin cancers provided a great impact on clinical practice. Despite these advances, NMSCs are still the most common malignancy in humans and melanoma still shows a rising incidence and a poor prognosis when diagnosed at an advanced stage. Efforts are required to underlie the genetic and clinical heterogeneity of melanoma and NMSCs, leading to an optimization of the management of affected patients. The clinical implications of the impact of germline MC1R variants in melanoma and NMSCs’ risk, together with the additional risk conferred by somatic mutations in other peculiar genes, as well as the role of MC1R screening in skin cancers’ prevention will be addressed in the current review.

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MC1R CpG island regulates MC1R expression and is methylated in a subset of melanoma tumours

Cited by 7 publications

References 22 publications

Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer

Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer

MC1R Is a Prognostic Marker and Its Expression Is Correlated with MSI in Colorectal Cancer

Behind the Scene: Exploiting MC1R in Skin Cancer Risk and Prevention

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