title: Genome-wide DNA methylation profile of leukocytes from melanoma patients with and without CDKN2A mutations.
abstract: Melanoma is a highly aggressive cancer, accounting for up to 75% of skin cancer deaths. A small proportion of melanoma cases can be ascribed to the presence of highly penetrant germline mutations, and approximately 40% of hereditary melanoma cases are caused by CDKN2A mutations. The current study sought to investigate whether the presence of germline CDKN2A mutations or the occurrence of cutaneous melanoma would result in constitutive genome-wide DNA methylation changes. The leukocyte methylomes of two groups of melanoma patients (those with germline CDKN2A mutations and those without CDKN2A mutations) were analyzed together with the profile of a control group of individuals. A pattern of DNA hypomethylation was detected in the CDKN2A-negative patients relative to both CDKN2A-mutated patients and controls. Additionally, we delineated a panel of 90 CpG sites that were differentially methylated in CDKN2A-mutated patients relative to controls. Although we identified a possible constitutive epigenetic signature in CDKN2A-mutated patients, the occurrence of reported SNPs at the detected CpG sites complicated the data interpretation. Thus, further studies are required to elucidate the impact of these findings on melanoma predisposition and their possible effect on the penetrance of CDKN2A mutations.
authors.affiliation: International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Érica  Sara Souza
authors.initials: É
authors.lastname: de Araújo
authors.affiliation: International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil; Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Fabio Albuquerque
authors.initials: FA
authors.lastname: Marchi
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Tatiane Cristina
authors.initials: TC
authors.lastname: Rodrigues
authors.affiliation: Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Henrique Cursino
authors.initials: HC
authors.lastname: Vieira
authors.affiliation: International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Hellen
authors.initials: H
authors.lastname: Kuasne
authors.affiliation: International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil; Department of Oncogenetics, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Maria Isabel Waddington
authors.initials: MI
authors.lastname: Achatz
authors.affiliation: Department of Skin Cancer, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Luciana Facure
authors.initials: LF
authors.lastname: Moredo
authors.affiliation: Department of Skin Cancer, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Bianca Costa Soares
authors.initials: BC
authors.lastname: de Sá
authors.affiliation: Department of Skin Cancer, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: João Pereira
authors.initials: JP
authors.lastname: Duprat
authors.affiliation: Department and Institute of Psychiatry, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Helena Paula
authors.initials: HP
authors.lastname: Brentani
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.affiliation: International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil; Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: ana.krepischi@gmail.com.
authors.forename: Ana Cristina Victorino
authors.initials: AC
authors.lastname: Krepischi
mesh_terms: D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007962:Leukocytes; D008297:Male; D008545:Melanoma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
keywords: CDKN2A; DNA methylation; Leukocytes; Melanoma; melanoma epigenetics