Genomic imbalances and changes in the methylation profile in the progression of the sporadic basal breast cancer: from primary tumor to metastases

• Grant number: 10/12139-5
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2011
• End date: February 28, 2013
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ana Cristina Victorino Krepischi
• Grantee: Ana Cristina Victorino Krepischi
• Host Institution: Hospital A C Camargo. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Cancer is a complex disease resulting from the accumulation of multiple somatic genetic alterations leading to changes of specific molecular pathways such as cell cycle control, apoptosis, differentiation and angiogenesis. Chromosomal abnormalities are very frequent genomic changes in cancer, and recent studies show that variations in the copy number of submicroscopic segments of DNA (copy number variation or CNV) events are also prevalent in various tumor types. A field of major study on the cancer genetics is distinguishing mutations responsible for tumor initiation process those important for tumor progression, and ultimately determine which mutations produce metastases. A comparative analysis between paired samples of the same tumor at different stages may provide clues of this process, since the mutation profiles are altered during the progression of primary tumors to metastases. Moreover, tumor cells also undergo major changes in the methylation pattern, with direct consequences on gene expression. Therefore, an integrated analysis encompassing genomics research (detection of submicroscopic genomic imbalances or chromosome alterations), and pattern of methylation can lead to a wider understanding, enabling to examine the interplay of different mechanisms of the gene expression control during carcinogenesis. This project proposes the study of genomic imbalances and methylation changes in the progression of a group of basal-like breast tumors. (AU)