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Editorial
Tumor suppressor BRCA1 prevents the development of several cancers, mainly breast and ovarian cancer. The main function of BRCA1 is the repair of DNA damage through homology recombination.1,2 The disruption of this BRCA1 function leads to the development of several oncological diseases, in particular, breast cancer, ovarian cancer and also non-small cell lung cancer. Recently, it became clear that BRCA1 can serve as a prognostic marker of the course of several oncological diseases and as a predictive marker of platinum-based therapy. Since the discovery of BRCA1 in early 1990 extensive studies of its biological function and mechanisms of its expression were carried out. Together with its associated proteins BRCA1 is involved in the repair of DNA double strand breaks through homologous recombination mechanism.2 Fine tuning of BRCA1 protein level is important for its balanced function in homologous recombination and therefore in the maintenance of genomic stability. Several molecular mechanisms of BRCA1 gene alterations and BRCA1 gene expression regulation were revealed. These mechanisms include germinal and sporadic mutations in BRCA1 gene,3 epigenetic mechanisms of the disruption of BRCA1 gene expression including methylation of CpG islands4,5 and covalent histone modifications in the promoter and coding region of BRCA1 gene, regulation with transcription factors ,6 loss of one allele of BRCA1 gene (so called loss of heterozigosity, LOH)7 and possibly amplification of BRCA1 gene.8 It has been demonstrated that these mechanisms could be the cause of BRCA1 function disruption and further could lead to the development of cancer.
In addition to well studied biological function of BRCA1 in homologous recombination and mechanisms of regulation of its expression, recently the role of BRCA1 as a biomarker of several oncological diseases emerged. It was shown that decreased levels of BRCA1 protein and mRNA often correlated with the development of breast and ovarian cancer and that the level of BRCA1 protein and mRNA could predict favorable/unfavorable course of the disease.9 Therefore, BRCA1 could function as a prognostic marker of the disease course. Moreover, it was demonstrated that decreased levels of BRCA1 protein and mRNA correlated with decreased resistance to platinum-based chemotherapy.10‒12 Therefore, BRCA1 could be a predictive marker of platinum chemotherapy efficiency. Taken together, BRCA1 perfectly corresponds to the definition of the biomarker. The biomarker has three main characteristics that include, first of all, a defined biological function, second, quantitative methods of its detection and third, the availability of patient cohorts of reasonable size to be studied. Firstly, it has defined biological function participating in the repair of DNA double strand breaks via homologous recombination. Secondly, there are several very precise methods allowing to measure quantities of BRCA1 protein and mRNA. Thirdly, patient cohorts of reasonable size are available for analysis. Altogether, BRCA1 protein emerges in recent years as the prognostic marker of the course of oncological diseases and as the predictive marker of the efficiency of platinum-based chemotherapy that is extensively used in the treatment of BRCA1-dependent cancers.
Acknowledgements
Dr. Elena A. Shestakova holds a position of Senior Research Scientist, PhD at N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation.
Conflict of interest
Author declares that there is no conflict of interest.
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