CRITICAL ANALYSIS OF CLINICAL FEATURES AND GENETIC ANCESTRY OF PATIENTS WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE 2 AND CARRIERS OF THE GENETIC VARIANTS RET V804L AND RET V804M

• Grant number: 23/18438-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2024
• Effective date (End): July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Lucas Leite Cunha
• Grantee: Felipe Rodrigues Betoni
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/02752-6 - Multiple Endocrine Neoplasia type 2 (MEN 2) and Medullary Thyroid Carcinoma (TCM): new issues in developmental biology, genetics, immunology, epidemiology, mechanisms of disease and clinical management, AP.TEM

Abstract

The medullary thyroid carcinoma (MTC) may be associated with Multiple Endocrine Neoplasia type 2 (MEN2) when it results from germline mutations in the RET proto-oncogene. Our hypothesis is that the geographic spread of the pathogenic variants V804L and V804M in the RET gene throughout the Brazilian territory may be attributed to a founder effect. The aim of our project is to describe the molecular epidemiology of the pathogenic variants V804M and V804L of the RET gene through clinical analysis and genetic ancestry. This is a cross-sectional analytical study in the field of translational medicine. Patients diagnosed clinically with MEN2 caused by the pathogenic variants V804L and V804M of the RET gene will be included. These patients will undergo active search for relevant clinical information in their medical records. In addition to clinical data, peripheral blood will be collected for DNA extraction and analysis of haplotypes related to the RET gene. Haplotype similarity analysis will identify if these pathogenic variants share a common ancestor and estimate the age of the establishment of these variants. We will build a database compiling information from all patients enrolled in the project. This database will include demographic, clinical, ethnographic, anatomopathological, and molecular information. With the follow-up time for each patient, we will determine whether the patient has experienced recurrence and whether the patient is alive at the time of assessment. The primary outcome in this study will be death from any cause and death due to MTC, allowing the establishment of overall survival of patients. The secondary outcome in this study will be recurrence, metastasis, or disease progression. Our results may provide information on the main expected clinical characteristics in MEN2 patients with the V804L and V804M variants of the RET gene. Consequently, we may identify prognostic markers in these patients, aiding clinical management and decision-making. Furthermore, our results will contribute to a better understanding of the ethnogenetic profile and historical aspects of the ancestry of MEN2 patients in the Brazilian territory.