Analysis of the CDKN1A, CDKN1B, CDKN2B and CDKN2C genes in multiple endocrine neoplasias type 1 and 2.

• Grant number: 09/15386-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2010
• End date: April 30, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Candida Barisson Villares Fragoso
• Grantee: Rodrigo de Almeida Toledo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Multiple endocrine neoplasias (MENs) are tumoral familial syndromes which involve several endocrine glands (pituitary, parathyroids, thyroid, endocrine pancreas and adrenal). Patients with MEN type 1 (MEN1) usually carry inactivating mutations in the MEN1 gene, while patients with MEN type 2 (MEN2) usually carry activating mutations in the RET proto-oncogene. Recently, patients with MENs but not carrying MEN1 and RET mutations were reported with rare germline mutations in the CDKN1A, CDKN1B, CDKN2B and CDKN2C tumor suppressor genes, which encodes for the cyclin-dependent kinase inhibitors (p15, p18, p21 and p27, respectively). The role of these genes in the clinical features of patients harboring disease-causing RET or MEN1 mutations has not been investigated so far. In the current study, we sought to analyze these new MEN-related tumor suppressor genes in RET- and MEN1-mutated patients, in order to clarify whether they play a role in the susceptibility and tumorigenesis of endocrine tumors in these patients.

Scientific publications

(19)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

LOURENCO, JR., DELMAR M.; COUTINHO, FLAVIA L.; TOLEDO, RODRIGO A.; GONCALVES, TATIANA DENCK; MONTENEGRO, FABIO L. M.; TOLEDO, SERGIO P. A.. Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1. Clinics, v. 67, n. 1, p. 99-108, 2012. (09/15386-6)

DE MENEZES MONTENEGRO, FABIO LUIZ; LOURENCO JUNIOR, DELMAR MUNIZ; TAVARES, MARCOS ROBERTO; ARAP, SERGIO SAMIR; NASCIMENTO JUNIOR, CLIMERIO PEREIRA; MASSONI NETO, LEDO MAZZEI; D'ALESSANDRO, ANDRE; TOLEDO, RODRIGO ALMEIDA; COUTINHO, FLAVIA LIMA; BRANDAO, LENINE GARCIA; et al. Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center. Clinics, v. 67, n. 1, p. 131-139, 2012. (09/15386-6)

YAO, LI; SCHIAVI, FRANCESCA; CASCON, ALBERTO; QIN, YUEJUAN; INGLADA-PEREZ, LUCIA; KING, ELIZABETH E.; TOLEDO, RODRIGO A.; ERCOLINO, TONINO; RAPIZZI, ELENA; RICKETTS, CHRISTOPHER J.; et al. Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas. JAMA, v. 304, n. 23, p. 2611-2619, DEC 15 2010. (09/15386-6)

QUEDAS, ELISANGELA P. S.; LONGUINI, VIVIANE C.; SEKIYA, TOMOKO; COUTINHO, FLAVIA L.; TOLEDO, SERGIO P. A.; TANNURI, UENIS; TOLEDO, RODRIGO A.. RET haplotype, not linked to the C620R activating mutation, associated with Hirschsprung disease in a novel MEN2 family. Clinics, v. 67, n. 1, p. 57-61, 2012. (09/15386-6)

PERONI, CIBELE N.; HAYASHIDA, CESAR Y.; NASCIMENTO, NANCY; LONGUINI, VIVIANE C.; TOLEDO, RODRIGO A.; BARTOLINI, PAOLO; BOWERS, CYRIL Y.; TOLEDO, SERGIO P. A.. Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice. Clinics, v. 67, n. 3, p. 8-pg., 2012-01-01. (09/15386-6)

DE MENEZES MONTENEGRO, FABIO LUIZ; LOURENCO JUNIOR, DELMAR MUNIZ; TAVARES, MARCOS ROBERTO; ARAP, SERGIO SAMIR; NASCIMENTO JUNIOR, CLIMERIO PEREIRA; MASSONI NETO, LEDO MAZZEI; D'ALESSANDRO, ANDRE; TOLEDO, RODRIGO ALMEIDA; COUTINHO, FLAVIA LIMA; BRANDAO, LENINE GARCIA; et al. Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center. Clinics, v. 67, p. 9-pg., 2012-01-01. (09/15386-6)

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, JAN 2014. (09/15386-6, 09/11942-1)

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, JUN 2014. (09/15386-6, 09/11942-1, 13/01476-9)

AGRAWAL, NISHANT; JIAO, YUCHEN; SAUSEN, MARK; LEARY, REBECCA; BETTEGOWDA, CHETAN; ROBERTS, NICHOLAS J.; BHAN, SHEETAL; HO, ALLEN S.; KHAN, ZUBAIR; BISHOP, JUSTIN; et al. Exomic Sequencing of Medullary Thyroid Cancer Reveals Dominant and Mutually Exclusive Oncogenic Mutations in RET and RAS. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 98, n. 2, p. E364-E369, FEB 2013. (09/15386-6)

PERONI, CIBELE N.; HAYASHIDA, CESAR Y.; NASCIMENTO, NANCY; LONGUINI, VIVIANE C.; TOLEDO, RODRIGO A.; BARTOLINI, PAOLO; BOWERS, CYRIL Y.; TOLEDO, SERGIO P. A.. Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice. Clinics, v. 67, n. 3, p. 265-272, 2012. (09/15386-6)

TOLEDO, RODRIGO A.; SEKIYA, TOMOKO; LONGUINI, VIVIANE C.; COUTINHO, FLAVIA L.; LOURENCO, JR., DELMAR M.; TOLEDO, SERGIO P. A.. Narrowing the gap of personalized medicine in emerging countries: the case of multiple endocrine neoplasias in Brazil. Clinics, v. 67, n. 1, p. 3-6, 2012. (09/15386-6)

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, 2012. (09/15386-6, 09/11942-1)

YAO, LI; SCHIAVI, FRANCESCA; CASCON, ALBERTO; QIN, YUEJUAN; INGLADA-PEREZ, LUCIA; KING, ELIZABETH E.; TOLEDO, RODRIGO A.; ERCOLINO, TONINO; RAPIZZI, ELENA; RICKETTS, CHRISTOPHER J.; et al. Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, v. 304, n. 23, p. 9-pg., 2010-12-15. (09/15386-6)

QUEDAS, ELISANGELA P. S.; LONGUINI, VIVIANE C.; SEKIYA, TOMOKO; COUTINHO, FLAVIA L.; TOLEDO, SERGIO P. A.; TANNURI, UENIS; TOLEDO, RODRIGO A.. RET haplotype, not linked to the C620R activating mutation, associated with Hirschsprung disease in a novel MEN2 family. Clinics, v. 67, p. 5-pg., 2012-01-01. (09/15386-6)

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, p. 6-pg., 2012-01-01. (09/15386-6)

TOLEDO, RODRIGO A.; SEKIYA, TOMOKO; LONGUINI, VIVIANE C.; COUTINHO, FLAVIA L.; LOURENCO, DELMAR M., JR.; TOLEDO, SERGIO P. A.. Narrowing the gap of personalized medicine in emerging countries: the case of multiple endocrine neoplasias in Brazil. Clinics, v. 67, p. 4-pg., 2012-01-01. (09/15386-6)

COUTINHO, FLAVIA L.; LOURENCO, JR., DELMAR M.; TOLEDO, RODRIGO A.; MONTENEGRO, FABIO L. M.; TOLEDO, SERGIO P. A.. Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Clinics, v. 67, n. 1, p. 169-172, 2012. (09/15386-6)

TOLEDO, SERGIO P. A.; LOURENCO, JR., DELMAR M.; TOLEDO, RODRIGO A.. A differential diagnosis of inherited endocrine tumors and their tumor counterparts. Clinics, v. 68, n. 7, p. 1039-1056, 2013. (09/15386-6)

LOURENCO, JR., DELMAR M.; COUTINHO, FLAVIA L.; TOLEDO, RODRIGO A.; MONTENEGRO, FABIO L. M.; CORREIA-DEUR, JOYA E. M.; TOLEDO, SERGIO P. A.. Early-Onset, Progressive, Frequent, Extensive, and Severe Bone Mineral and Renal Complications in Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism. Journal of Bone and Mineral Research, v. 25, n. 11, p. 2382-2391, NOV 2010. (09/15386-6)