title: DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients.
abstract: In melanoma development, oncogenic process is mediated by genetic and epigenetic mutations, and few studies have so far explored the role of DNA methylation either as predisposition factor or biomarker. We tested patient samples for germline CDKN2A methylation status and found no evidence of inactivation by promoter hypermethylation. We have also investigated the association of clinical characteristics of samples with the DNA methylation pattern of twelve genes relevant for melanomagenesis. Five genes (BAP1, MGMT, MITF, PALB2, and POT1) presented statistical association between blood DNA methylation levels and either CDKN2A-mutation status, number of lesions, or Breslow thickness. In tumors, five genes (KIT, MGMT, MITF, TERT, and TNF) exhibited methylation levels significantly different between tumor groups including acral compared to nonacral melanomas and matched primary lesions and metastases. Our data pinpoint that the methylation level of eight melanoma-associated genes could potentially represent markers for this disease both in peripheral blood and in tumor samples.
authors.affiliation: International Research Center, A.C.Camargo Cancer Center, Rua Taguá 440, 01508010 São Paulo, SP, Brazil.
authors.forename: Érica S S
authors.initials: ÉS
authors.lastname: de Araújo
authors.affiliation: International Research Center, A.C.Camargo Cancer Center, Rua Taguá 440, 01508010 São Paulo, SP, Brazil.
authors.forename: Dimitrius T
authors.initials: DT
authors.lastname: Pramio
authors.affiliation: Federal Technological University of Paraná, Avenida Alberto Carazzai 1640, 86300000 Cornélio Procópio, PR, Brazil.
authors.forename: André Y
authors.initials: AY
authors.lastname: Kashiwabara
authors.affiliation: School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, 05508000 São Paulo, SP, Brazil.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Pennacchi
authors.affiliation: School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, 05508000 São Paulo, SP, Brazil.
authors.forename: Silvya S
authors.initials: SS
authors.lastname: Maria-Engler
authors.affiliation: International Research Center, A.C.Camargo Cancer Center, Rua Taguá 440, 01508010 São Paulo, SP, Brazil ; Department of Oncogenetics, A.C.Camargo Cancer Center, Rua Professor Antônio Prudente 211, 01509010 São Paulo, SP, Brazil.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Achatz
authors.affiliation: Department of Pathology, A.C.Camargo Cancer Center, Rua Professor Antônio Prudente 211, 01509010 São Paulo, SP, Brazil.
authors.forename: Antonio H J F M
authors.initials: AH
authors.lastname: Campos
authors.affiliation: Skin Cancer Department, A.C.Camargo Cancer Center, Rua Professor Antônio Prudente 211, 01509010 São Paulo, SP, Brazil.
authors.forename: João P
authors.initials: JP
authors.lastname: Duprat
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508090 São Paulo, SP, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.affiliation: International Research Center, A.C.Camargo Cancer Center, Rua Taguá 440, 01508010 São Paulo, SP, Brazil.
authors.forename: Dirce M
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: International Research Center, A.C.Camargo Cancer Center, Rua Taguá 440, 01508010 São Paulo, SP, Brazil ; Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508090 São Paulo, SP, Brazil.
authors.forename: Ana C V
authors.initials: AC
authors.lastname: Krepischi
mesh_terms: D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology