Author: Zhang Meng Ran Release Date: 2018-09-26
According to an oncology study published online by the British journal Nature recently, the American team of scientists has performed an unprecedented classification of thousands of BRCA1 gene variants by function, reporting the results of the carcinogenic risk analysis of BRCA1 gene variants. This "functional score" has clinical significance for the interpretation of genetic testing for screening for breast cancer and ovarian cancer risk.
BRCA1 is a human tumor suppressor gene that is responsible for maintaining the stability of the cell genome and preventing the accumulation of genetic mutations that regulate cell proliferation and tumor growth. Mutations in which BRCA1 loses function are thought to be associated with predisposition to early-onset breast and ovarian cancer. Up to now, although there have been thousands of BRCA1 gene mutations, many of them have been classified as “unknown mutationsâ€, which poses a huge challenge to the assessment of human cancer risk.
To clarify these unclear variations, one of the methods is to detect whether the expression of the variant gene has the function of restoring DNA repair, which is part of the tumor suppression process. In light of this, University of Washington researcher Jay Schinder and colleagues used genome editing techniques to perform nearly 4,000 single nucleotide variants (SNV) functions on 13 exons critical for BRCA1 gene function. Evaluation and subsequent cell viability assays were performed in 20 million human haploid (HAP1) cells.
Finally, the team identified about 300 SNVs that interfered with expression and more than 400 missense mutations in SNV (which led to changes in the Amino Acid sequence of the protein) and found that these variants have no actual function (without destroying the original function of the gene) . These functional scores are closely related to the clinical assessment of known pathogenic or benign variants.
The researchers point out that the HAP1 cell line may not be the physiologically optimal model compared to other cell lines, but the data is highly correlated with clinical evaluation. The National Cancer Institute scientists affirmed the important value of “functional scores†for the classification of mutations, and concluded that the results can be directly applied to the interpretation of BRCA1 genetic screening.
Source: Technology Daily
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