Genome-wide DNA methylation profile of leukocytes from melanoma patients with and without CDKN2A mutations

Autor(es):Mostrar menos -

Souza de Araujo, Erica Sara ^[1] ; Marchi, Fabio Albuquerque ^{[2, 1]} ; Rodrigues, Tatiane Cristina ^[3] ; Vieira, Henrique Cursino ^[2] ; Kuasne, Hellen ^[1] ; Waddington Achatz, Maria Isabel ^{[4, 1]} ; Moredo, Luciana Facure ^[5] ; Soares de Sa, Bianca Costa ^[5] ; Duprat, Joao Pereira ^[5] ; Brentani, Helena Paula ^[6] ; Rosenberg, Carla ^[3] ; Carraro, Dirce Maria ^[1] ; Victorino Krepischi, Ana Cristina ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, Int Ctr Res, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Math & Stat, BR-05508090 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, BR-05508090 Sao Paulo - Brazil

^[4] AC Camargo Canc Ctr, Dept Oncogenet, Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Dept Skin Canc, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, BR-05508090 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental and Molecular Pathology; v. 97, n. 3, p. 425-432, DEC 2014.
• Citações Web of Science: 3

Resumo

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. (C) 2014 The Authors. Published by Elsevier Inc. (AU)

• Processo FAPESP: 13/07480-8 - Fatores genéticos e epigenéticos na etiologia do melanoma cutâneo
• Beneficiário: Ana Cristina Victorino Krepischi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/13963-9 - Perfil global de metilação do genoma na síndrome do melanoma familial
• Beneficiário: Érica Sara Souza de Araújo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 08/57887-9 - Instituto Nacional de Oncogenômica
• Beneficiário: Luiz Paulo Kowalski
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/04313-2 - Fatores genéticos e de meio ambiente de risco para o desenvolvimento de melanoma na América Latina
• Beneficiário: Gilles Landman
• Modalidade de apoio: Auxílio à Pesquisa - Regular