Genetic and epigenetic aspects in gastric carcinogenesis

• Grant number: 09/07145-9
• Support Opportunities: Research Projects - Thematic Grants
• Duration: December 01, 2009 - August 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marilia de Arruda Cardoso Smith
• Grantee: Marilia de Arruda Cardoso Smith
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated 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

(8)

(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)

WISNIESKI, FERNANDA; GERALDIS, JAQUELINE CRUZ; SANTOS, LEONARDO CAIRES; LEAL, MARIANA FERREIRA; CALCAGNO, DANIELLE QUEIROZ; GIGEK, CAROLINA OLIVEIRA; CHEN, ELIZABETH SUCHI; ANAUATE, ANA CAROLINA; ARTIGIANI, RICARDO; DEMACHKI, SAMIA; et al. ifferential regulation of LRRC37A2 in gastric cancer by DNA methylatio. Epigenetics, v. 17, n. 1, FEB 2021. (07/02470-3, 09/07145-9, 16/19953-6, 17/06227-8, 10/11174-1)

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; et al. Identification of suitable reference genes for miRNA expression normalization in gastric cancer. Gene, v. 621, p. 59-68, JUL 20 2017. (13/23900-7, 12/14768-5, 09/07145-9)

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; et al. 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. (09/07145-9)

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. (09/07145-9)

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. (10/11174-1, 09/07145-9)

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; et al. 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. (09/07145-9)

WISNIESKI, FERNANDA; GERALDIS, JAQUELINE CRUZ; SANTOS, LEONARDO CAIRES; LEAL, MARIANA FERREIRA; CALCAGNO, DANIELLE QUEIROZ; GIGEK, CAROLINA OLIVEIRA; CHEN, ELIZABETH SUCHI; ANAUATE, ANA CAROLINA; ARTIGIANI, RICARDO; DEMACHKI, SAMIA; et al. Differential regulation of LRRC37A2 in gastric cancer by DNA methylation. Epigenetics, v. 17, n. 1, p. 7-pg., 2021-02-07. (07/02470-3, 17/06227-8, 09/07145-9, 10/11174-1, 16/19953-6)

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; et al. 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. (09/07145-9)