Genes regulated by DNA methylation are involved in distinct phenotypes during melanoma progression and are prognostic factors for patients

Author(s):Show less -

Papaiz, Debora D'Angelo ; Rius, Flavia Eichemberger ; Ayub, Ana Luisa Pedroso ; Origassa, Clarice S. ; Gujar, Hemant ; Pessoa, Diogo de Oliveira ; Reis, Eduardo Moraes ; Nsengimana, Jeremie ; Newton-Bishop, Julia ; Mason, Christopher E. ; Weisenberger, Daniel J. ; Liang, Gangning ; Jasiulionis, Miriam Galvonas

• Document type: Journal article
• Source: MOLECULAR ONCOLOGY; v. 16, n. 9, p. 18-pg., 2022-02-04.

Abstract

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. (AU)

• FAPESP's process: 19/23480-4 - Novel strategies for eliminating residual tumor cells using epigenetic therapy
• Grantee: Miriam Galvonas Jasiulionis
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/13663-0 - Integrating gene and microRNA expression, methylome and hidroxymethylome data from different phases of melanoma progression.
• Grantee: Miriam Galvonas Jasiulionis
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/20775-0 - Non-coding RNAs involved with melanoma genesis and progression
• Grantee: Miriam Galvonas Jasiulionis
• Support Opportunities: Regular Research Grants