Recent advances in molecular genetics of breast cancer

Breast cancer is among the most common tumors affecting women. It is charac terized by a number of genetic aberrations. Sonic 5-10% or cases are though t to be inherited. The hereditary breast and ovarian cancer syndrome includ es genetic alterations of various susceptibility genes, particularly BRCA1 and BRCA2. Breast tumors of patients with germ-line mutations in the BRCA1 and BRCA2 genes have more genetic defects than sporadic breast tumors. Here we review new findings in the function of BRCA1 gene function. Accumulatio n of somatic genetic changes during tumor progression map follows a specifi c and more aggressive pathway of chromosome damage in these individuals. A major BRCA1 downstream target gene is the DNA damage-responsive gene GADD45 . Induction of BRCA1 triggers apoptosis by activation of c-Jun N-terminal k inase/stress-activated protein kinase (JNK/SAPK). BRCA1 interacts with SWI/ SNF, a chromatin remodeling complex important in gene expression. Recent ad vances in genomics and bio-informatics, particularly in DNA-sequencing appr oaches and DNA-chip technology are expected to improve identification of sm all molecules, which might be drugable targets. New knowledge about the gen etic portrait of breast tumor is coming from differential gene expression p rofiling using microarrays. Human genome studies, as well as development of "DNA chips," provide a window for observing patterns of gene activity in c ells, which will contribute to more accurate cancer classification. However , substantial work connected with analytical and statistical tools must sti ll be carried out to confirm the function of differentially expressed genes . Knowledge of the molecular characteristics of breast tumor has already st arted to make possible the identification of breast cancer patients who cou ld benefit from therapies that target those features. Progress in basic res earch into signaling provides the opportunity to attack at least some signa l-transduction targets involved in proliferation, survival, invasion, angio genesis, metastasis, and resistance. Exciting knowledge in breast cancer bi ology is rapidly accumulating in parallel with recent developments in ratio nal selection and validation of relevant targets that provide unique opport unities for development of "intelligent" therapeutics.