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Global genomic methylation profile in familial melanoma syndrome

Grant number: 12/13963-9
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2012
Effective date (End): August 31, 2015
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Ana Cristina Victorino Krepischi
Grantee:Érica Sara Souza de Araújo
Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Melanoma is a highly aggressive skin cancer with an incidence rate that has been rising worldwide. Most melanomas are sporadic events, but the risk of developing this cancer significantly increases in individuals with family history of melanoma. There are two highly penetrant melanoma predisposition genes: CDKN2A (encoding p16 and p14) and CDK4. However, part of the familial melanoma cases has no identifiable germline mutation in these genes, suggesting the involvement of yet unknown loci. Deregulation of DNA methylation plays an important role in the development and progression of cancer. Tumor cells exhibit aberrant genome-wide methylation patterns (called epimutations) compared to their counterpart normal tissues, leading to anomalous gene expression. Recently, constitutive epimutations have been pointed as an alternative mechanism of cancer predisposition. In view of the unknown etiology of the majority familial melanomas cases and the importance of DNA methylation in tumorigenesis, the goal of this project is evaluating the epigenome of patients classified as familial melanoma syndrome cases. We intend to define if germline epigenetic changes can contribute to the pathogenesis of melanoma. The approach will be to study the genome-wide DNA methylation pattern using high resolution microarrays aiming to identify genes with aberrant methylation profile and delineate the biological networks affected. Subsequently, the relevant genes will be analyzed regarding their DNA methylation pattern and genic expression in a group of melanomas derived from these patients. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE ARAUJO, ERICA S. S.; KASHIWABARA, ANDRE Y.; ACHATZ, MARIA I. W.; MOREDO, LUCIANA F.; DE SA, BIANCA C. S.; DUPRAT, JOAO P.; ROSENBERG, CARLA; CARRARO, DIRCE M.; KREPISCHI, ANA C. V.. LINE-1 hypermethylation in peripheral blood of cutaneous melanoma patients is associated with metastasis. Melanoma Research, v. 25, n. 2, p. 173-177, . (13/07480-8, 12/13963-9)
SOUZA DE ARAUJO, ERICA SARA; MARCHI, FABIO ALBUQUERQUE; RODRIGUES, TATIANE CRISTINA; VIEIRA, HENRIQUE CURSINO; KUASNE, HELLEN; WADDINGTON ACHATZ, MARIA ISABEL; MOREDO, LUCIANA FACURE; SOARES DE SA, BIANCA COSTA; DUPRAT, JOAO PEREIRA; BRENTANI, HELENA PAULA; et al. Genome-wide DNA methylation profile of leukocytes from melanoma patients with and without CDKN2A mutations. Experimental and Molecular Pathology, v. 97, n. 3, p. 425-432, . (13/07480-8, 12/13963-9, 08/57887-9, 07/04313-2)
DE ARAUJO, ERICA S. S.; PRAMIO, DIMITRIUS T.; KASHIWABARA, ANDRE Y.; PENNACCHI, PAULA C.; MARIA-ENGLER, SILVYA S.; ACHATZ, MARIA I.; CAMPOS, ANTONIO H. J. F. M.; DUPRAT, JOAO P.; ROSENBERG, CARLA; CARRARO, DIRCE M.; et al. DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients. BIOMED RESEARCH INTERNATIONAL, v. 2015, p. 8-pg., . (12/13963-9, 13/10785-5, 13/07480-8)
DE ARAUJO, ERICA S. S.; PRAMIO, DIMITRIUS T.; KASHIWABARA, ANDRE Y.; PENNACCHI, PAULA C.; MARIA-ENGLER, SILVYA S.; ACHATZ, MARIA I.; CAMPOS, ANTONIO H. J. F. M.; DUPRAT, JOAO P.; ROSENBERG, CARLA; CARRARO, DIRCE M.; et al. DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients. BIOMED RESEARCH INTERNATIONAL, . (13/07480-8, 13/10785-5, 12/13963-9)

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