Open AccessGenes regulated by DNA methylation are involved in distinct phenotypes during melanoma progression and are prognostic factors for patients
Author(s) -
Papaiz Debora D’Angelo,
Rius Flávia Eichemberger,
Ayub Ana Luísa Pedroso,
Origassa Clarice S.,
Gujar Hemant,
Pessoa Diogo de Oliveira,
Reis Eduardo Moraes,
Nsengimana Jérémie,
NewtonBishop Julia,
Mason Christopher E.,
Weisenberger Daniel J.,
Liang Gangning,
Jasiulionis Miriam Galvonas
Publication year - 2022
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13185
Subject(s) - epigenetics , biology , dna methylation , cancer research , melanoma , malignant transformation , tumor progression , phenotype , transcriptome , gene , methylation , regulation of gene expression , gene expression , genetics
In addition to mutations, epigenetic alterations are important contributors to malignant transformation and tumor progression. The aim of this work was to identify epigenetic events in which promoter or gene body DNA methylation induces gene expression changes that drive melanocyte malignant transformation and metastasis. We previously developed a linear mouse model of melanoma progression consisting of spontaneously immortalized melanocytes, premalignant melanocytes, a nonmetastatic tumorigenic, and a metastatic cell line. Here, through the integrative analysis of methylome and transcriptome data, we identified the relationship between promoter and/or gene body DNA methylation alterations and gene expression in early, intermediate, and late stages of melanoma progression. We identified adenylate cyclase type 3 ( Adcy3 ) and inositol polyphosphate 4‐phosphatase type II ( Inpp4b ), which affect tumor growth and metastatic potential, respectively. Importantly, the gene expression and DNA methylation profiles found in this murine model of melanoma progression were correlated with available clinical data from large population‐based primary melanoma cohorts, revealing potential prognostic markers.