engleski

Recent advances in molecular genetics of breast cancer

Breast cancer is among the most common tumors affecting women. It is characterized by a number of genetic aberrations. Five to 10% of all cases are estimated to be inherited. The hereditary breast and ovarian cancer syndrome includes genetic alterations of various susceptibility genes, particularly BRCA 1 and BRCA 2. Breast tumors of patients with germ-line mutations in the BRCA 1 and BRCA 2 gene have an increase of additional genetic defects compared with sporadic breast tumors. Here we review some new findings in the function of BRCA 1 gene function. Accumulation of somatic genetic changes during tumor progression map follows a specific and more aggressive pathway of chromosome damage in these individuals. A major BRCA 1 downstream target gene is the DNA damage-responsive gene GADD 45. Induction of BRCA 1 triggers apoptosis through activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). BRCA 1 interacts with a complex SWI/SNF, a chromatin remodeling complex, important in gene expression. Recent advances in genomics and bioinformatics, particularly in DNA-sequencing approaches and DNA-chip technology are expected to improve identification of small molecules, which might be drugable targets. New knowledge about the genetic portrait of breast tumor is coming from differential gene expression profiling using microarrays. Human genome studies, as well as development of “DNA chips”, provide a window for observing patterns of gene activity in cells, which will contribute to more accurate cancer classification. However, there is a lot of work connected with analytical and statistical tools, which has to be done in order to validate function of differentially expressed genes. Knowledge of the molecular characteristics of breast tumor already started to make possible identification of those breast cancer patients who could benefit from therapies that target those features. Progress in basic research in signaling provides the opportunity to attack at least some signal-transduction targets involved in proliferation, survival, invasion, angiogenesis, metastasis and resistance. Exciting knowledge in breast cancer biology is rapidly accumulating in parallel with recent developments in rational selection and validation of relevant targets that provide unique opportunities for development of “intelligent” therapeutics.

breast cancer; molecular genetics; BRCA1; signaling; "intelligent therapy"

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