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Whole exome sequencing for the investigation of novel genetic causes of metastatic Pheochromocytomas and Paragangliomas

Grant number: 21/11240-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date: November 01, 2021
End date: October 31, 2025
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Madson Queiroz Almeida
Grantee:Felipe Freitas de Castro
Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:19/15873-6 - Investigation of new genetic, clinical and pathological aspects of endocrine arterial hypertension, AP.TEM

Abstract

Pheochromocytomas and Paragangliomas are neuroendocrine tumors derived from chromaffin cells. Approximately 15-20% of Pheochromocytomas and Paragangliomas are classified as metastatic, defined by the presence of tumor in non-chromaffin tissues. To date, at least 20 susceptibility genes for PPGLs have been reported. Germline pathogenic variants in SDHB gene are the most well-established risk factor to predict metastatic disease in 40-50% of cases. In our Institution, germline genetic alterations in SDHB were found in 25% of the cases, SDHD 3%, NF1 3%, SDHA 3% and MET 3%. Therefore, 63% of the metastatic Pheochromocytomas and Paragangliomas of our cohort remain without genetic diagnosis after investigation using a gene target sequencing panel by massive parallel sequencing. The aim of this project is to investigate novel genetic causes of metastatic Pheochromocytomas and Paragangliomas. The specific aims are: 1) to perform whole exome sequencing of germline and tumor DNA of 20 patients with metastatic pheochromocytoma or paraganglioma; 2) to correlate the genetic findings with clinical and follow-up data; 3) to perform functional studies to evaluate the pathogenicity of the rare and in silico deleterious germline variants in new candidate genes. (AU)

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Scientific publications (7)
(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)
FREITAS-CASTRO, FELIPE; SANTANA, LUCAS S.; FAGUNDES, GUSTAVO F. C.; LOBATO, EDUARDO C.; AFONSO, ANA CAROLINE F.; NAKAMURA, IZABEL T.; LEDESMA, FELIPE L.; SOARES, IBERE C.; MENDONCA, BERENICE B.; LATRONICO, ANA CLAUDIA; et al. SLC25A11, a Novel Gene Associated With Carney-Stratakis Syndrome. JOURNAL OF THE ENDOCRINE SOCIETY, v. 9, n. 5, p. 9-pg., . (19/15873-6, 21/10363-0, 24/03610-9, 21/11240-9)
FAGUNDES, GUSTAVO F. C.; FREITAS-CASTRO, FELIPE; SANTANA, LUCAS S.; LEDESMA, FELIPE L.; PETENUCI, JANAINA; AFONSO, ANA CAROLINE F.; PEREIRA, CAIO A. A.; MACIEL, ANA ALICE W.; SOARES, IBERE C.; GOMES, NATHALIA L.; et al. Insights into the genetic landscape of pheochromocytomas and paragangliomas in a Brazilian cohort. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 192, n. 1, p. 14-pg., . (19/15873-6, 21/10363-0, 21/11240-9, 21/09879-1)
MORI, GUSTAVO H.; FAGUNDES, GUSTAVO F. C.; SANTANA, LUCAS S.; FREITAS-CASTRO, FELIPE; AFONSO, ANA CAROLINE F.; LOURENCO, DELMAR M.; PEREIRA, MARIA ADELAIDE A.; TANNO, FABIO Y.; SROUGI, VICTOR; CHAMBO, JOSE L.; et al. Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 69, p. 6-pg., . (19/15873-6, 21/10363-0, 21/11240-9)
FAGUNDES, GUSTAVO F. C.; FREITAS-CASTRO, FELIPE; SANTANA, LUCAS S.; AFONSO, ANA CAROLINE F.; PETENUCI, JANAINA; FUNARI, MARIANA F. A.; GUIMARAES, AUGUSTO G.; LEDESMA, FELIPE L.; PEREIRA, MARIA ADELAIDE A.; VICTOR, CAROLINA R.; et al. Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 10-pg., . (19/15873-6, 21/10101-5, 21/11240-9, 21/10363-0)
MACIEL, ANA ALICE W.; DANILOVIC, DEBORA L. S.; SOARES, IBERE C.; FREITAS, THAIS C.; OKUBO, JESSICA; FAGUNDES, GUSTAVO F. C.; FREITAS-CASTRO, FELIPE; SANTANA, LUCAS S.; GUIMARAES, AUGUSTO G.; CALSAVARA, VINICIUS F.; et al. Association Between Papillary Thyroid Cancer and Primary Aldosteronism in Individuals With Hypertension. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 12-pg., . (21/10101-5, 21/11240-9, 21/10363-0, 19/15873-6, 21/09879-1)
FREITAS-CASTRO, FELIPE; ALMEIDA, MADSON Q.. Personalized management for phaeochromocytomas and paragangliomas in Latin America: A genetic perspective. BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, v. 39, n. 1, p. 8-pg., . (19/15873-6, 21/11240-9)
FREITAS, THAIS C.; MACIEL, ANA ALICE W.; FAGUNDES, GUSTAVO F. C.; PETENUCI, JANAINA; SANTANA, LUCAS S.; GUIMARAES, AUGUSTO G.; FREITAS-CASTRO, FELIPE; SROUGI, VICTOR; TANNO, FABIO Y.; CHAMBO, JOSE L.; et al. Efficacy of Oral Furosemide Test for Primary Aldosteronism Diagnosis. JOURNAL OF THE ENDOCRINE SOCIETY, v. 8, n. 1, p. 10-pg., . (21/10101-5, 21/11240-9, 21/10363-0, 19/15873-6, 21/09879-1)