Validation of CREBBP, NOTCH2, ATM and GNAS gene mutations in uterine leiomyosarcoma cells

• Grant number: 23/05721-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Kátia Cândido Carvalho
• Grantee: Micaela Giovana Alves Pinheiro da Cunha
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Uterine leiomyosarcomas are rare, aggressive and difficult to treat tumors. Given this scenario, new therapeutic approaches have been investigated. Several studies show that genetic mutations are closely associated with cellular transformation, greater metastatic potential and, consequently, worse prognosis, however, despite recent efforts, the molecular aspects of uterine leiomyosarcomas remain poorly defined, lacking elucidative research. In this sense, in work previously carried out by our group, several gene mutations were identified in samples of uterine leiomyosarcomas and leiomyomas. We believe that these alterations are related to the process of tumoral malignancy, since they were detected in tumor suppressor or proto-oncogenic genes. Thus, the objective of this project is to validate the presence and frequency of genetic alterations in CREBBP, NOTCH2, ATM and GNAS by genetic sequencing using the Sanger method in culture of immortalized cells from uterine leiomyosarcomas. The results will be tabulated using SPSS version 20.0 (IL, USA), Graph Pad Prism® 5.0 (CA, USA) and Excel for Windows XP software, for descriptive and inferential analysis (according to the nature of the variables). After grouping, the data will be submitted to homogeneity evaluation with subsequent application of specific statistical test. All results will be considered significant when p<0.05.