title: Quantitative analysis of CDKN2A methylation, mRNA, and p16(INK4a) protein expression in children and adolescents with Burkitt lymphoma: biological and clinical implications.
abstract: CDKN2A is a tumor suppressor gene critical in the cell cycle regulation. Little is known regarding the role of CDKN2A methylation in the pathogenesis of Burkitt lymphoma (BL). CDKN2A methylation was investigated using pyrosequencing in 51 tumor samples. p16(INK4a) mRNA and protein levels were measured using real-time PCR and immunohistochemistry, respectively. CDKN2A methylation was detectable in 72% cases. Nuclear expression of p16(INK4a) was not detected in 41% cases. There was an association between methylation and absence of CDKN2A mRNA (P=0.003). In conclusion, CDKN2A methylation occurs at a high frequency suggesting a role in BL pathogenesis and potential therapeutic implications.
authors.affiliation: Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Marcela Cristina S
authors.initials: MC
authors.lastname: Robaina
authors.affiliation: Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Roberta Soares
authors.initials: RS
authors.lastname: Faccion
authors.affiliation: Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Viviane Oliveira
authors.initials: VO
authors.lastname: Arruda
authors.affiliation: Divisão de Patologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Lidia Maria Magalhães
authors.initials: LM
authors.lastname: de Rezende
authors.affiliation: Programa de Hematologia e Oncologia Pediátrica, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Gisele Moledo
authors.initials: GM
authors.lastname: Vasconcelos
authors.affiliation: Serviço de Hematologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Alexandre Gustavo
authors.initials: AG
authors.lastname: Apa
authors.affiliation: Consultoria em Patologia, Botucatu, São Paulo, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bacchi
authors.affiliation: Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. Electronic address: cklumb@inca.gov.br.
authors.forename: Claudete Esteves
authors.initials: CE
authors.lastname: Klumb
mesh_terms: D000293:Adolescent; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm
keywords: Burkitt lymphoma; CDKN2A; Methylation; Pyrosequencing; Survival; p16(INK4a)