Recently identified CHEK2 Y390C mutation facilitates early breast cancer development


In China, breast cancers tend to occur at younger age and higher percentage than that in Caucansians. However, the mutations of BRCA1/2 and CHEK2 germline, which are reported highly associate with breast cancer, are rarely found in Chinese breast cancer patients. Wang et al. identified a missense variant Y390C of CHEK2 that related to tumorigenesis in high-risk breast cancer patients. The article was published on Oncogene, recently.


The patients carry CHEK2 Y390C mutation tend to develop breast cancer early, despite those with family history. Mechanically, researchers found the codon change at loci Y390, a residue of CHEK2's kinase domain, significantly destroys CHEK2 activity, which is confirmed by functional analysis of CHEK2 Y390C mutation. The mutant CHEK2 Y390C protein unable to inactivate CDC25A or to activate p53, p21 and Puma expression after DNA damage. Furthermore, it leads to the deregulation of cell cycle checkpoint and response of cell apoptosis, which in turn contribute to tumorigeneisis. The findings provide a better view on genetic mutations that facilitate breast tumorigenesis, and suggest CHEK2 Y390C variant act as a promising target for breast cancer monitoring, prevention and management.


Oncogene. 2015 Jan 26. doi: 10.1038/onc.2014.443. 

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