BRCA1 and BRCA2 are considered as tumour suppressor genes but mutations of these genes are selectively increase the risk of breast and ovarian cancers, compare to other type of tissue cancers.is there any reason for tissue specificity?
Hi Kamalathasan.
The organs are all expressing ER during embryonic development, certain cell phenotype differentiation and maintenance of the adult organs. And BRCA genes may be involved in ER signaling. Thus, Epigenetic regulation of BRCA genes appears to be related to ER-activated other gene regulation.
Regards.
BRCA1 has important DNA repair role in almost any cell type. However, it is known that there is a tissue-specific cancer predisposition associated with BRCA1. If there is loss of BRCA1 function, breast and ovaries are the two places that preferentially develop cancers.
If you compare tissues of BRCA1 mutation carriers versus non-carriers you find that gene expression-related stress is higher in BRCA1 mutation carriers, this stress is only higher in luminal epithelial cells, where BRCA1-related breast tumors originate; within the luminal epithelial cells, the stress is higher in estrogen-responsive genes. Gene expression-related stress is a result of cells expressing genes to carry out functions. This process sometimes damages the genetic blueprint, DNA, resulting in abnormal structures that scientists label as stress. Accordingly, breasts and ovaries are two major estrogen-responsive sites in a woman's body and this zooming in on the stress location is the connection between BRCA1 dysfunction and breast and ovarian cancers.
...............results suggest that women from BRCA mutation–negative, site-specific breast cancer families are not at increased risk for ovarian cancer.
https://academic.oup.com/jnci/article/97/18/1382/2521398
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