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Genetic and epigenetic aspects in gastric carcinogenesis

Grant number: 09/07145-9
Support type:Research Projects - Thematic Grants
Duration: December 01, 2009 - August 31, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Marilia de Arruda Cardoso Smith
Grantee:Marilia de Arruda Cardoso Smith
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Ismael Dale Cotrim Guerreiro da Silva ; Monica Vannucci Nunes Lipay ; Rommel Mario Rodríguez Burbano ; Sylvia Satomi Takeno Herrero
Associated scholarship(s):13/23900-7 - Genetic and epigenetic evaluation in gastric cancer, BP.PD
12/03506-0 - Molecular changes associated with childhood abuse: a MeDIP-Seq study, BE.PQ
10/11174-1 - Genetic and epigenetic evaluation in gastric cancer, BP.PD
09/11251-9 - Epigenetic regulation in gastric cancer, BP.MS
09/08046-4 - Study of histone acetylation status in gastric carcinogenesis, BP.DR

Abstract

Gastric cancer is the fourth most prevalent and the second cause of cancer death worldwide. Nowadays, Brazil is in the fourth most prevalent in gastric cancer in Latin America. Alterations in methylation patterns or chromatin remodeling have been involved in carcinogenesis due to their crucial role in regulation mechanisms. Moreover, cytogenetic abnormalities have been associated with neoplasia, including gastric cancer. The investigation of these genetic and epigenetic mechanisms might lead to better diagnosis, prognosis and therapeutic purposes. To analyze whether DNA methylation and/or histone methylation and acetylation are the main mechanisms of regulation in cancer process, two gastric cell lines will be treated with 5-Aza-2'-deoxycytidine and trichostatin and then, analyzed by microarray and proteomic assays in the current study. After microarray and proteome screening, expression of differentially expressed genes will be evaluated in 50 normal and in 50 tumoral gastric samples by qRT-PCR. Promoter methylation and/or histone H3K9 methylation and acetylation status will be evaluated by MS-HRM and ChIP, respectively. This study also aims to verify if histone methylation and/or acetylation are involved in the regulation of previously studied genes in our laboratory. Expression of genes involved in DNA methylation and histone modifications machinery will also be measured. Gene expression and epigenetic modifications will be associated to sex, age, tumor location, H. pylori, tumor extension, limph node metastasis, distant metastasis and histopathologic type of gastric adenocarcinoma. In addition, CGH assays will be used to identify cytogenetic abnormalities. The current study will originate new and better biological information, as biomarkers, which will enable a better understanding of etiology and physiopathology of this neoplasia with potential medical implication. (AU)

Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ANAUATE, ANA CAROLINA; LEAL, MARIANA FERREIRA; WISNIESKI, FERNANDA; SANTOS, LEONARDO CAIRES; GIGEK, CAROLINA OLIVEIRA; CHEN, ELIZABETH SUCHI; GERALDIS, JAQUELINE CRUZ; CALCAGNO, DANIELLE QUEIROZ; ASSUMPCAO, PAULO PIMENTEL; DEMACHKI, SAMIA; ARASAKI, CARLOS HARUO; LOURENCO, LAERCIO GOMES; ARTIGIANI, RICARDO; BURBANO, ROMMEL RODRIGUEZ; CARDOSO SMITH, MARILIA ARRUDA. Identification of suitable reference genes for miRNA expression normalization in gastric cancer. Gene, v. 621, p. 59-68, JUL 20 2017. Web of Science Citations: 7.
WISNIESKI, FERNANDA; LEAL, MARIANA FERREIRA; CALCAGNO, DANIELLE QUEIROZ; SANTOS, LEONARDO CAIRES; GIGEK, CAROLINA OLIVEIRA; CHEN, ELIZABETH SUCHI; ARTIGIANI, RICARDO; DEMACHKI, SAMIA; ASSUMPCAO, PAULO PIMENTEL; LOURENCO, LAERCIO GOMES; BURBANO, ROMMEL RODRIGUEZ; SMITH, MARILIA CARDOSO. BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer. Journal of Cellular Biochemistry, v. 118, n. 4, p. 869-877, APR 2017. Web of Science Citations: 6.
CALCAGNO, DANIELLE QUEIROZ; TAKENO, SYLVIA SANTOMI; GIGEK, CAROLINA OLIVEIRA; LEAL, MARIANA FERREIRA; WISNIESKI, FERNANDA; CHEN, ELIZABETH SUCHI; THOMAZ ARAUJO, TAISSA MAIRA; LIMA, ELEONIDAS MOURA; MELARAGNO, MARIA ISABEL; DEMACHKI, SAMIA; ASSUMPCAO, PAULO PIMENTEL; BURBANO, ROMMEL RODRIGUEZ; SMITH, MARILIA CARDOSO. Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines. WORLD JOURNAL OF GASTROENTEROLOGY, v. 22, n. 43, p. 9506-9514, NOV 21 2016. Web of Science Citations: 4.
MELLO, ADRIANO AZEVEDO; LEAL, MARIANA FERREIRA; REY, JUAN ANTONIO; PINTO, GIOVANNY REBOUCAS; LAMARAO, LETICIA MARTINS; MONTENEGRO, RAQUEL CARVALHO; NEGREIROS NUNES ALVES, ANA PAULA; ASSUMPCAO, PAULO PIMENTEL; BORGES, BARBARA DO NASCIMENTO; SMITH, MARILIA CARDOSO; BURBANO, ROMMEL RODRIGUEZ. Deregulated Expression of SRC, LYN and CKB Kinases by DNA Methylation and Its Potential Role in Gastric Cancer Invasiveness and Metastasis. PLoS One, v. 10, n. 10 OCT 13 2015. Web of Science Citations: 12.
CALCAGNO, DANIELLE QUEIROZ; GIGEK, CAROLINA OLIVEIRA; CHEN, ELIZABETH SUCHI; BURBANO, ROMMEL RODRIGUEZ; CARDOSO SMITH, MARILIA DE ARRUDA. DNA and histone methylation in gastric carcinogenesis. WORLD JOURNAL OF GASTROENTEROLOGY, v. 19, n. 8, p. 1182-1192, FEB 28 2013. Web of Science Citations: 54.
GIGEK, CAROLINA OLIVEIRA; CHEN, ELIZABETH SUCHI; CALCAGNO, DANIELLE QUEIROZ; WISNIESKI, FERNANDA; BURBANO, ROMMEL RODRIGUEZ; CARDOSO SMITH, MARILIA ARRUDA. Epigenetic mechanisms in gastric cancer. Epigenomics, v. 4, n. 3, p. 279-294, JUN 2012. Web of Science Citations: 72.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.