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Analysis of CDKN1B/p27kip1 gene in patients with Multiple Endocrine Neoplasia Type 2

Grant number: 09/11942-1
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): February 01, 2010
Effective date (End): January 31, 2014
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Sergio Pereira de Almeida Toledo
Grantee:Tomoko Sekiya
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


In recent years, our group have studied clinically and genetically patients with Multiple Endocrine Neoplasms (MENs), including the MEN type 2 (MEN2). The MEN2 is an inherited tumor syndrome that potentially affects the thyroid gland, leading to Medullary Thyroid Carcinoma (MTC); parathyroids, leading to primary hyperparathyroidism (HPT); and the adrenal medulla, leading to pheochromocytoma (PHEO) The vast majority of cases with MEN2 (> 90%) harbor a germline activating mutation in the RET proto-oncogene. The impact of molecular diagnosis of RET in the clinical and surgical management of MEN2 patients is impressive. The consensus on MEN and MTC recommended that the RET mutation carriers should be submitted to early and preventive total thyroidectomy that currently consists in the only approach that can guarantee prevention of MTC. Recent studies have shown that genes involved in the cell cycle control, as the CDKN2C (which encodes the protein p18INK4) and CDKN1B (which encodes the protein p27Kip1), may be also involved in the molecular pathogenesis of MEN2-related tumors. Our group we have previously described a RET variant V648I could influence the clinical feature of C634Y RET mutation carriers. In the present study, we aim to investigate whether CDKN2C/p18INK4 and CDKN1B/p27Kip1 genes recently associated with MEN2 tumors play a role as potential phenotype modulators in patients with MEN2. Forty RET-mutated patients will be included in the study.We will assess the clinical features of these patients and compare them with the genotypes of CDKN2C/p18INK4 and CDKN1B/ p27Kip1 to clarify whether there is a correlation of these new genes with possible modified susceptibility for MTC, PHE and/or HPT in MEN2. (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)
SEKIYA, TOMOKO; BRONSTEIN, MARCELLO D.; BENFINI, KATIUSCIA; LONGUINI, VIVIANE C.; JALLAD, RAQUEL S.; MACHADO, MARCIO C.; GONCALVES, TATIANA D.; OSAKI, LUCIANA H.; HIGASHI, LEONARDO; VIANA-, JR., JOSE; et al. p27 variant and corticotropinoma susceptibility: a genetic and in vitro study. Endocrine-Related Cancer, v. 21, n. 3, p. 395-404, . (09/15386-6, 09/11942-1, 13/01476-9)
GONCALVES, TATIANA D.; TOLEDO, RODRIGO A.; SEKIYA, TOMOKO; MATUGUMA, SERGIO E.; MALUF FILHO, FAUZE; ROCHA, MANOEL S.; SIQUEIRA, SHEILA A. C.; GLEZER, ANDREA; BRONSTEIN, MARCELO D.; PEREIRA, MARIA A. A.; et al. Penetrance of Functioning and Nonfunctioning Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 in the Second Decade of Life. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 99, n. 1, p. E89-E96, . (09/15386-6, 09/11942-1)
TAVARES, MARCOS R.; TOLEDO, SERGIO P. A.; MONTENEGRO, FABIO L. M.; MOYSES, RAQUEL A.; TOLEDO, RODRIGO A.; SEKYIA, TOMOKO; CERNEA, CLAUDIO R.; BRANDAO, LENINE G.. Surgical approach to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2. Clinics, v. 67, n. 1, p. 149-154, . (09/15386-6, 09/11942-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SEKIYA, Tomoko. CDKN1B/p27kip1 gene analysis in patients with multiple endocrine neoplasia type 2 (MEN2). 2013. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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