Biochemical and molecular investigation of primary aldosteronism

• Grant number: 22/04899-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2023
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Margaret de Castro
• Grantee: Leonardo Kenzo Maeda
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/03989-6 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS), AP.TEM

Abstract

Adrenal tumors are rare and include tumors of the medulla (pheochromocytomas/paragangliomas - Pheo/PGLs) and adrenal cortex (adenomas - ACT and carcinomas - ACC), which may be non-secretory or secretory (simple virilizing, ACTH-independent Cushing's syndrome, aldosternomas or mixed ones). Screening for primary aldosteronism (PA), one of the main endocrine causes of arterial hypertension, is essential because the patient has the potential to be cured after treatment and with reduced costs in the follow-up of these patients. From a molecular point of view, our laboratory has a complete arsenal for the molecular diagnosis of PA, as it has investigated the molecular pathogenesis of pituitary and adrenal tumors (Fapesp Thematic Project no. Next-generation sequencing (NGS)" and intends, with this project, to improve the investigation of genetic causes of aldosteronomas. Thus, we will evaluate somatic mutations in the genes KCNJ5, CACNA1H, CLCN2, ATP1A1, ATP2B3, and CTNNB1 in patients with PA due to APA, unilateral and bilateral hyperplasia. Also, we aim to identify new candidate genes for PA, through exome genotyping in germline DNAs (blood) paired with tumor DNA/hyperplastic tissue by large-scale sequencing, in those patients negative for mutations already described. Expected results are better diagnostic accuracy, better follow-up and management of patients with this adrenal disease, in addition to advancing knowledge in this area.