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Methylation pattern and HES1, Wnt5a and RET gene expressions in familial and sporadic medullary thyroid carcinoma

Grant number: 12/02465-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2012
Effective date (End): February 28, 2017
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Magnus Régios Dias da Silva
Grantee:Mirian Gonçalves Cardoso
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):14/26505-4 - Driver gene DNA methylation in medullary thyroid cancer, BE.EP.DD


Epigenetic modifications are defined as heritable changes in gene expression that are not accompanied by changes in the nucleotide sequence of DNA. The relationship between epigenetic mechanisms and tumorigenesis was first verified through of whole genome hypomethylation in carcinomas. Abnormal methylation appears to play an important role in differentiated thyroid carcinomas derived from the follicular epithelium (papillary and follicular), indeed several of the tumor suppressor genes are epigenetically silenced, but little is known about the methylation profile of genes related to Medullary Thyroid Carcinoma (MTC), a tumor derived from parafollicular cells that produce calcitonin as biochemical marker. We propose to study the methylation pattern and expression of the RET oncogene, a major player of MAPK pathway, the tumor suppressor genes WNT5A of NOTCH, and HES1 of WNT5A signaling pathways. Preliminary data obtained from MTC cell line (TT) have pointed out hypomethylation of HES1 and hypermethylation of WNT5A, suggesting an epigenetic influence in cell line progression. As a second goal we proposed to study surgical specimens of CMT from patients with different clinical evolutions but carrying the same mutation. Therefore, we intend to verify whether methylation pattern of one of these genes could also play a role in vivo on the presentation variability and prognosis associated to MTC. (AU)

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Scientific publications
(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)
NASCIMENTO, FABRICIO P.; CARDOSO, MIRIAN G.; LINDSEY, SUSAN C.; KUNII, ILDA S.; VALENTE, FLAVIA O. F.; KIZYS, MARINA M. L.; DELCELO, ROSANA; CAMACHO, CLEBER P.; MACIEL, RUI M. B.; DIAS-DA-SILVA, MAGNUS R. Analysis of somatic mutations in BRAF, CDKN2A/p16 and PI3KCA in patients with medullary thyroid carcinoma. MOLECULAR MEDICINE REPORTS, v. 13, n. 2, p. 1653-1660, FEB 2016. Web of Science Citations: 2.
KIZYS, MARINA M. L.; NESI-FRANCA, SUZANA; CARDOSO, MIRIAN G.; HARADA, MICHELLE Y.; MELO, MARIA CLARA C.; CHIAMOLERA, MARIA IZABEL; DIAS-DA-SILVA, MAGNUS R.; MACIEL, RUI M. B. The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis. JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, v. 27, n. 3-4, p. 317-322, MAR 2014. Web of Science Citations: 3.

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