title: CDKN2A (p14(ARF)/p16(INK4a)) and ATM promoter methylation in patients with impalpable breast lesions.
abstract: Early detection of breast cancer increases the chances of cure, but the reliable identification of impalpable lesions is still a challenge. In spite of the advances in breast cancer detection, the molecular basis of impalpable lesions and the corresponding circulating biomarkers are not well understood. Impalpable lesions, classified by radiologists according to the Breast Imaging Reporting and Data System in the categories 3 and 4, can be either benign or malignant (slow growing or aggressive). In this article, we report the DNA methylation pattern in CDKN2A (p14(ARF)/p16(INK4a)) and in ATM gene promoters from 62 impalpable lesions, 39 peripheral blood samples, and 39 saliva samples, assessed by methylation-specific polymerase chain reaction method. ATM showed the greatest percentage of methylation in DNA from lesions (benign and malignant), blood (even with p16(INK4a)), and saliva, followed by p16(INK4a) and p14(ARF). Among the malignant cases, ATM promoter was the most hypermethylated in lesion DNA and in blood and saliva DNAs, and p14(ARF), the least. The highest percentage of p16(INK4a) methylation was found in the blood. Finally, our data are relevant because they were obtained using impalpable breast lesions from patients who were carefully recruited in 2 public hospitals of Rio de Janeiro.
authors.affiliation: Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro 20230-130, Brazil; Pós-Graduação em Ciências Médicas, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-170, Brazil; Laboratório de Marcadores Circulantes, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-170, Brazil.
authors.forename: Lucas
authors.initials: L
authors.lastname: Delmonico
authors.affiliation: Laboratório de Genômica Funcional de Bioinformática, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil.
authors.forename: Aline dos Santos
authors.initials: Ados S
authors.lastname: Moreira
authors.affiliation: Serviço de Radiologia, Hospital Universitário Gaffrée-Guinle, Rio de Janeiro 20270-004, Brazil.
authors.forename: Marco Felipe
authors.initials: MF
authors.lastname: Franco
authors.affiliation: Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro 20230-130, Brazil.
authors.forename: Eliane Barbosa
authors.initials: EB
authors.lastname: Esteves
authors.affiliation: Sociedade Brasileira Oncologia Clínica, Belo Horizonte, Minas Gerais 30120-010, Brazil.
authors.forename: Luciano
authors.initials: L
authors.lastname: Scherrer
authors.affiliation: Departamento de Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade Estadual do Rio de Janeiro, Rio de Janeiro 20550-900, Brazil.
authors.forename: Claúdia Vitória de Moura
authors.initials: CV
authors.lastname: Gallo
authors.affiliation: Serviço de Anatomia Patológica, Hospital Universitário Gaffrée-Guinle, Rio de Janeiro 20270-004, Brazil.
authors.forename: Cristina Moreira
authors.initials: CM
authors.lastname: do Nascimento
authors.affiliation: Pós-Graduação em Ciências Médicas, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-170, Brazil; Laboratório de Marcadores Circulantes, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-170, Brazil.
authors.forename: Maria Helena Faria
authors.initials: MH
authors.lastname: Ornellas
authors.affiliation: Serviço de Radiologia, Hospital Universitário Gaffrée-Guinle, Rio de Janeiro 20270-004, Brazil.
authors.forename: Carolina Maria
authors.initials: CM
authors.lastname: de Azevedo
authors.affiliation: Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro 20230-130, Brazil; Pós-Graduação em Ciências Médicas, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-170, Brazil; Laboratório de Marcadores Circulantes, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-170, Brazil. Electronic address: galvesbrown@gmail.com.
authors.forename: Gilda
authors.initials: G
authors.lastname: Alves
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000032:analysis* / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D019942:Genes, p16; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; DNA methylation; Impalpable lesions; p14(ARF); p16(INK4a)