Evaluation of TERT mutation frequency associated with breast cancer progression

• Grant number: 16/19944-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2017
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Márcia Maria Chiquitelli Marques Silveira
• Grantee: Sara de Freitas Abrão
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Breast cancer is the leading cause of cancer mortality among women. Metastases are responsible for about 90% of deaths in patients affected by this tumor type, indicating the invasion and metastasis in the important role of spread of cancer. Metastasis is the process that most affects clinical management of cancer patients. Despite the knowledge that the metastatic process proceeds multiple sequential steps, the molecular basis of the pathways governing these steps still remain unclear. Recent work has shown that the reactivation of telomerase expression is referred to as a common feature in many types of human solid tumors. However, the molecular genetic basis of this process is still very poorly understood. It is known that the presence of somatic mutations in the promoter region of the TERT gene (human telomerase reverse transcriptase) is common in many tumors. However, in the context of breast cancer this scenario is still largely unexplored. Thus, the aim of this study is to identify the frequency of somatic mutations of the promoter region of the TERT gene and loss of ATRX expression, and evaluate frequency of rs2853669 polymorphism in TERT mutated (-245bp A> G) in Brazilian patients with breast cancer. The frequency of mutations will be performed by PCR followed by pyrosequencing, while the presence of the polymorphism will be evaluated by direct sequencing (Sanger). Clinical and molecular data will be organized into a database using SPSS version 19. The mean and frequency of mutations will be analyzed using statistical and mathematical environment R. Finally, using Fisher's exact test will evaluate the prognostic value of frequency these mutations and the presence of the polymorphism in patients with breast cancer. (AU)