Molecular aspects involved in the emergence of triple-negative breast cancer patients with or without germline mutation in BRCA1

• Grant number: 14/22589-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2015
• End date: November 30, 2018
• Field of knowledge: Biological Sciences - Genetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Dirce Maria Carraro
• Grantee: Kivvi Duarte de Mello Nakamura
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Triple-negative breast câncer (TNBC), characterizad by lack of significant expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), is a most aggressive subtype of breast cancer with poor prognosis and affects approximately 15% of cases of breast cancer. Among the major susceptibility genes for breast cancer are BRCA1 / BRCA2, which are the most prevalent. It has been observed by several groups large association between TN tumor mediated by BRCA1-germline mutation, especially in young women. In this context, we aim in this project is to investigate the transcriptional profile in TN tumor associated or not with the BRCA1-germline mutation in young patients. Thus, by using next-generation sequencing, we will investigate the global transcriptional profile by RNAseq, using tumor and adjacent normal tissue from TN young patients being or not BRCA1-carriers. The identified alterations will be validated in an independent group of TN samples previously tested for BRCA1 and data will be integrated with other data of sequencing exoma already generated by group, enabling more complete analysis of tumorigenesis of TN. Overall the results of this project, will allow better understanding of the transcriptional alterations mediated by BRAC1-germline mutation and, therefore, enable news discoveries to therapeutic targets for the treatment of TN breast cancer young patients. (AU)