title: CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas.
abstract: CDKN1A is a tumor suppressor gene involved in gastric carcinogenesis and is a potential target for histone deacetylase inhibitor-based therapies. Upregulation of CDKN1A is generally observed in several cell lines after histone deacetylase inhibitor treatment; however, little is known about the histone acetylation status associated with this gene in clinical samples, including gastric tumor tissue samples. Therefore, our goal was to quantify the H3K9 and H4K16 acetylation levels associated with three CDKN1A regions in 21 matched pairs of gastric adenocarcinoma and corresponding adjacent non-tumor samples by chromatin immunoprecipitation and to correlate these data with the gene expression. Our results demonstrated that the -402, -20, and +182 CDKN1A regions showed a significantly increased acetylation level in at least one of the histones evaluated (p < 0.05, for all comparisons), and these levels were positively correlated in gastric tumors. However, an inverse correlation was detected between both H3K9 and H4K16 acetylation at the -402 CDKN1A region and mRNA levels in gastric tumors (r = -0.51, p = 0.02; r = -0.60, p < 0.01, respectively). Furthermore, increased H4K16 acetylation at the -20 CDKN1A region was associated with gastric tumors of patients without lymph node metastasis (p = 0.04). These results highlight the complexity of these processes in gastric adenocarcinoma and contribute to a better understanding of CDKN1A regulation in carcinogenesis.
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, 04023900, Brazil. fernandawis@yahoo.com.br.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Wisnieski
authors.affiliation: Núcleo de Pesquisas em Oncologia, Hospital João de Barros Barreto, Universidade Federal do Pará, Avenida Mundurucus, 4487, Belém, 66073000, Brazil.
authors.forename: Danielle Queiroz
authors.initials: DQ
authors.lastname: Calcagno
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, 04023900, Brazil.|Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, Rua Borges Lagoa, 783, São Paulo, 04038032, Brazil.
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, 04023900, Brazil.
authors.forename: Leonardo Caires
authors.initials: LC
authors.lastname: Santos
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, 04023900, Brazil.
authors.forename: Carolina Oliveira
authors.initials: CO
authors.lastname: Gigek
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, 04023900, Brazil.
authors.forename: Elizabeth Suchi
authors.initials: ES
authors.lastname: Chen
authors.affiliation: Núcleo de Pesquisas em Oncologia, Hospital João de Barros Barreto, Universidade Federal do Pará, Avenida Mundurucus, 4487, Belém, 66073000, Brazil.
authors.forename: Sâmia
authors.initials: S
authors.lastname: Demachki
authors.affiliation: Departamento de Patologia, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, 04023000, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Artigiani
authors.affiliation: Núcleo de Pesquisas em Oncologia, Hospital João de Barros Barreto, Universidade Federal do Pará, Avenida Mundurucus, 4487, Belém, 66073000, Brazil.
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.affiliation: Disciplina de Gastroenterologia Cirúrgica, Departamento de Cirurgia, Universidade Federal de São Paulo, Rua Napoleão de Barros, 715, São Paulo, 04024002, Brazil.
authors.forename: Laércio Gomes
authors.initials: LG
authors.lastname: Lourenço
authors.affiliation: Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correia, 01, Belém, 66075110, Brazil.
authors.forename: Rommel Rodríguez
authors.initials: RR
authors.lastname: Burbano
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, 04023900, Brazil.
authors.forename: Marília Cardoso
authors.initials: MC
authors.lastname: Smith
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D047369:Chromatin Immunoprecipitation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D012333:RNA, Messenger
keywords: CDKN1A; Gastric cancer; Gene expression regulation; Histone acetylation