Molecular genetics of breast cancer progression

Somatic changes in the genome of breast cancer cells include amplifications , deletions and gene mutations. Several chromosome regions harboring known oncogenes are found amplified in breast tumors. Despite the high number of chromosome regions deleted in breast tumors the functional relationship to known genes at these locations and cancer growth is mainly undiscovered. Mu tations in two tumor suppressor genes (TSG) have been described in a subset of breast carcinomas. These TSG are the TP53, encoding the p53 transcripti on factor, and the CDH1, encoding the cadherin cell adhesion molecule. Brea st tumors of patients with a germ-line mutation in the BRCA1 or BRCA2 gene have an increase of additional genetic defects compared with sporadic breas t tumors. This higher frequency of genetic aberrations could pinpoint genes that selectively promote tumor progression in individuals predisposed to b reast cancer due to BRCA1 or BRCA2 germ-line mutations. Accumulation of som atic genetic changes during tumor progression map follow a specific and mor e aggressive pathway of chromosome damage in these individuals. Although th e sequence of molecular events in the progression of breast tumor is poorly understood the detected genetic alterations fit the model of multistep car cinogenesis in both sporadic and hereditary breast cancer. This review will focus on the genetic lesions within the breast cancer cell.