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Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS)

Grant number: 14/03989-6
Support type:Research Projects - Thematic Grants
Duration: March 01, 2017 - February 28, 2022
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Margaret de Castro
Grantee:Margaret de Castro
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Léa Maria Zanini Maciel ; Sonir Roberto Rauber Antonini
Assoc. researchers:Ana Valeria Castro ; Ayrton Custodio Moreira ; Fabiano Pinto Saggioro ; Helio Rubens Machado ; Houtan Noushmehr ; Luciano Neder Serafini ; Paula Condé Lamparelli Elias ; Wilson Araújo da Silva Junior
Associated scholarship(s):19/08041-4 - Wnt/beta-catenin pathway in pediatric adrenocortical tumors, BP.IC
19/00860-6 - Uncovering pathophysiological and molecular mechanisms involvedIn tumorigenesis by platforms for next-generation sequencing (NGS), BP.PD
19/00849-2 - Uncovering pathophysiological and molecular mechanisms involvedIn tumorigenesis by platforms for next-generation sequencing (NGS), BP.PD
18/08210-8 - Next generation sequencing in pediatric adrenocortical tumors, BP.PD

Abstract

To elucidate the molecular pathogenesis of endocrine tumors, several studies have investigated the role of specific genes regulating the organ development, genes involved in tumorigenesis of other tissues, such as abnormalities in genes that lead to cycle progression and cell division (oncogenes) or genes that block the cell cycle (tumor suppressor genes), miRNAs, and large noncoding (lncRNAs). Significant advances have been observed in the molecular elucidation of various hereditary syndromes that occur with pituitary tumors [(McCune - Albright, Multiple endocrine neoplasia (MEN) type 1 and type 4, Carney's syndrome, and familial isolated pituitary adenoma (FIPA)]; with adrenal tumors (Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex, McCune-Albright, MEN1); and with thyroid tumors (MEN2, Hereditary medullar thyroid carcinoma). All these advances occurred due approaches based on candidate genes and linkage studies, but the molecular pathogenesis of sporadic endocrine tumors has not been completely clarified. The new platforms of next generation sequencing (NGS) present major advantages for the analysis of 1) exoma (Target-seq analysis) 2) epigenomic (either by chromatin immunoprecipitation (ChIP) or promoter DNA methylation analysis), and 3) transcriptome. Therefore, this project aims to use NGS technology to better understand the process of central nervous system (glyomas) and endocrine tumorigenesis. Tumoral tissues will be obtained from patients followed in the Hospital das Clinicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HCFMRP-USP). As controls, normal tissue samples will be obtained at CEMEL (Center of Forensic Medicine) from autopsies of patients with accidental or sudden death from cardiac causes. The NGS certainly will indicate new genes and/or new cell signaling pathways that may be keys of the enlightenment of endocrine tumorigenesis. (AU)

Scientific publications (5)
(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)
OLIVEIRA-SANTOS, ALECIA A.; SALVATORI, ROBERTO; NOGUEIRA, MONICA C.; BUENO, ANA C.; BARROS-OLIVEIRA, CYNTHIA S.; LEAL, ANGELA C. G. B.; MARINHO, CINDI G.; DAMASCENA, NAYRA P.; OLIVEIRA, DJANE A.; MELO, MANUELA A.; OLIVEIRA, CARLA R. P.; DA COSTA, FLAVIA O.; DOS SANTOS, JESSICA S. S.; SANTOS, PAULA F. C.; CAMPOS, VIVIANE C.; SANTOS, ELENILDE G.; MELO, ENALDO V.; BARBOSA, MEIRIELLY L. A.; ROCHA, IVINA E. S.; DE CASTRO, MARGARET; AGUIAR-OLIVEIRA, MANUEL H. Enteroendocrine Connections in Congenital Isolated GH Deficiency Due to a GHRH Receptor Gene Mutation. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 104, n. 7, p. 2777-2784, JUL 2019. Web of Science Citations: 0.
STECCHIN, MONICA F.; BRAID, ZILDA; MORE, CANDY B.; ARAGON, DAVI C.; CASTRO, MARGARET; MOREIRA, AYRTON C.; ANTONINI, SONIR R. Gonadotropin-dependent pubertal disorders are common in patients with virilizing adrenocortical tumors in childhood. ENDOCRINE CONNECTIONS, v. 8, n. 5, p. 579-589, MAY 2019. Web of Science Citations: 0.
DOLCE, LUCIANO G.; SILVA-JUNIOR, RUI M. P.; ASSIS, LEANDRO H. P.; NASCIMENTO, ANDREY F. Z.; ARAUJO, JACKELINE S.; MESCHEDE, INGRID P.; ESPREAFICO, ENILZA M.; DE GIUSEPPE, PRISCILA O.; MURAKAMI, MARIO T. Myosin Va interacts with the exosomal protein spermine synthase. BIOSCIENCE REPORTS, v. 39, n. 3 MAR 29 2019. Web of Science Citations: 1.
MOREIRA, AYRTON CUSTODIO; ANTONINI, SONIR RAUBER; DE CASTRO, MARGARET. A sense of time of the glucocorticoid circadian clock: from the ontogeny to the diagnosis of Cushing's syndrome. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 179, n. 1, p. R1-R18, JUL 2018. Web of Science Citations: 1.
DE SOUZA, CAMILA FERREIRA; SABEDOT, THAIS S.; MALTA, TATHIANE M.; STETSON, LINDSAY; MOROZOVA, OLENA; SOKOLOV, ARTEM; LAIRD, PETER W.; WIZNEROWICZ, MACIEJ; IAVARONE, ANTONIO; SNYDER, JAMES; DECARVALHO, ANA; SANBORN, ZACHARY; MCDONALD, KERRIE L.; FRIEDMAN, WILLIAM A.; TIRAPELLI, DANIELA; POISSON, LAILA; MIKKELSEN, TOM; CARLOTTI, JR., CARLOS G.; KALKANIS, STEVEN; ZENKLUSEN, JEAN; SALAMA, SOFIE R.; BARNHOLTZ-SLOAN, JILL S.; NOUSHMEHR, HOUTAN. A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence. CELL REPORTS, v. 23, n. 2, p. 637-651, APR 10 2018. Web of Science Citations: 17.

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