Study of the correlation between the mutational status of CTNNB1 and BRAF with the radiological presentation of Adamantinomatous Craniopharyngiomas

• Grant number: 23/06272-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Suely Kazue Nagahashi Marie
• Grantee: Guilherme José da Costa Borsatto
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/02988-7 - Decoding the impact of microenvironment and signaling pathways in health and disease in brain, adrenal gland and kidney, AP.TEM

Abstract

Craniopharyngiomas (CRF) are relatively rare benign neoplasms of the Central Nervous System, derived from remnants of the craniopharyngeal epithelial duct. Despite their histological characteristics, these tumors pose significant challenges in clinical and surgical management due to their proximity to the optic pathways, pituitary gland and stalk, third ventricle, and hypothalamus.There are two types of CRF: Papillary CRF (CPap) and Adamantinomatous CRF (CAda). Among these, CAda is more common (approximately 90% of CRF cases), predominantly affecting children and presenting calcifications and cystic components in 90% of cases. Recent genetic characterizations of this subtype have identified mutations in the ²-catenin gene (CTNNB1) in approximately 90% of tumors, resulting in the accumulation of this protein in specific cells within the tumor microenvironment. CAda represents the most prevalent non-neuroepithelial intracranial neoplasms in pediatric patients and is associated with the poorest quality of life scores among all intracranial tumors in children.Currently, the standard treatment consists of surgery and radiotherapy; however, both are associated with high morbidity. Over the past two decades, extensive research into the pathophysiological mechanisms and microenvironmental structure of CRF has provided promising prospects for targeted therapies. In the case of CPap, the discovery of the BRAFV600E mutation in approximately 80% of tumors has led to paradigm shifts in its treatment, with the application of inhibitors targeting the associated pathway. However, research on CAda is still in its early stages, despite being intense.Therefore, in the context of seeking molecular markers as therapeutic targets, it is necessary to perform a molecular diagnosis of CAda, particularly regarding mutations in BRAF and CTNNB1. However, the medical literature lacks non-invasive methods for characterizing the genetic alterations of these tumors. Hence, the study of imaging parameters as tools for characterizing molecular aspects and the tumor microenvironment becomes a key approach as a potential predictor of these mutations, taking into account radiological features that consider the current understanding of the pathophysiology of these tumors.