Genomic Instability and Breast Cancer Progression

Abstract

The genome of breast tumour cells is considered to be unstable, as reflected by multiple chromosomal and gene abnormalities. The molecular mechanism of genomic instability progression in breast cancer is poorly understood, but recent data suggest that mutated or overexpressed proteins affect the genome in several ways, including an abnormal number of centrosomes, inefficient DNA repair and unwanted telomere maintenance. Among these proteins are p53, Brca1, Brca2, Aurora kinase A, Myc and telomerase. The involved molecular networks include co-regulation with cell cycle checkpoints. p53 has been relatively well studied and is considered to be a guardian of the genome integrity. Myc seems to affect tumour pathogenesis in several ways, including increased proliferation and immortalisation of the cancer cells and induction of genomic instability. Aurora kinase A has been shown to control the centrosome number of cells and the segregation of the correct chromosomes to the daughter cells during mitosis. Genomic instability is high in some hereditary breast cancer, particularly in tumours of Brca1- and Brca2-mutation carriers, a finding that is in line with their role in DNA repair.