Enhancer of zeste 2 polycomb repressive complex 2 subunit polymorphisms in melanoma skin cancer risk.


Journal

Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549

Informations de publication

Date de publication:
10 2020
Historique:
received: 03 06 2020
revised: 29 07 2020
accepted: 30 07 2020
pubmed: 5 8 2020
medline: 26 10 2021
entrez: 5 8 2020
Statut: ppublish

Résumé

Melanoma is the most deadly skin cancer, and its incidence is growing. EZH2, a member of the Polycomb Group (PcGs) proteins family, plays an important biological role in the occurrence and development of melanoma. EZH2 germline genetic polymorphisms have not been yet evaluated in melanoma predisposition. Three hundred thirty sporadic Italian melanoma patients and 333 healthy volunteers were genotyped to analyse the association between EZH2 variants rs6950683, rs2302427, rs3757441, rs2072408 and melanoma risk. The functionality of rs6950683 alleles was investigated in keratinocytes (HaCat), melanoma cells (A375) and human embryonic kidney cells (HEK293), using promoter-reporter assays. Genotype distribution of SNPs showed that rs6950683T and rs3757441C alleles were positively associated with melanoma risk (P = .003 and .004, respectively). Haplotype analysis revealed that TCCA and CCCG haplotypes were associated with a higher risk of melanoma (P = .02 and .04, respectively). Functional assays demonstrated that allele rs6950683T reduce promoter activity in the three cell lines analysed compared to C allele. rs6950683T and rs3757441C alleles in the EZH2 gene appear positively associated with melanoma risk in the analysed population. In addition, we demonstrated for the first time the functional role of rs6950683 upstream polymorphism on EZH2 gene expression regulation.

Identifiants

pubmed: 32748461
doi: 10.1111/exd.14163
doi:

Substances chimiques

Enhancer of Zeste Homolog 2 Protein EC 2.1.1.43

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

980-986

Informations de copyright

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Auteurs

Francesca Belpinati (F)

Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.

Giovanni Malerba (G)

Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.

Melissa Dal Toè (M)

Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.

Laura Ceccuzzi (L)

Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.

Monica Rodolfo (M)

Melanoma and Sarcoma Surgery, Unit of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Albino Poli (A)

Department of Diagnostic and Public Health, Environmental and Occupational Medicine, Section of Hygiene and Preventive, University of Verona, Verona, Italy.

Alberto Turco (A)

Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.

Elisabetta Vergani (E)

Melanoma and Sarcoma Surgery, Unit of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Antonella Sangalli (A)

Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.

Macarena Gomez-Lira (M)

Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.

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