Breast Cancer and Paradigm of Genomic Instability

Genome instability could be defined as anelevated tendency for the genome to acquire geneticalterations; ranging from changes to the nucleotidesequence to chromosomal gain, loss orrearrangements. Accumulating evidence indicatesthat cell transformation is associated with genomeinstability leading to an imbalance between themechanisms of cell-cycle control and mutation rateswithin the genes. Genomic instability is broadlyclassified into microsatellite instability (MIN)associated with mutated phenotype, andchromosome instability (CIN) expressed as grosschromosomal abnormalities. The development ofcancers can be mediated through DNA repairmechanisms, genetic (or epigenetic) alterations inoncogenes and tumor suppressor genes that regulatecellular processes such as cell-proliferation,differentiation, death and genome stability. Genomicinstability is often associated with cancer and can beindicative of a poor prognosis for some types ofcancer. But, we still do not know clearly whether ۱genomic instability is a consequence of tumorprogression or an active process in tumor evolution.However, many new findings have highlightedcertain DNA repair pathways and cell cycle controlprocesses that have important consequences forgenomic stability and tumor cell biology.