|LETTER TO EDITOR
|Year : 2020 | Volume
| Issue : 2 | Page : 373-374
Study of BRCA mutation variations: Need of the hour
Rajesh Singh Laishram
Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Submission||04-Mar-2020|
|Date of Acceptance||05-Mar-2020|
|Date of Web Publication||19-Jun-2020|
Rajesh Singh Laishram
Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Laishram RS. Study of BRCA mutation variations: Need of the hour. Cancer Res Stat Treat 2020;3:373-4
Breast cancer is the most commonly diagnosed cancer in women and the second most common cause of death from cancer among women. The most well-known genes associated with hereditary cancer syndrome are the BRCA1/ 2 genes for hereditary breast and ovarian cancer syndrome (HBOC).
In the previous issue of the Journal, Chheda et al. in a study conducted in India reported their findings in which 160 women fulfilling the NCCN guidelines for genetic studies for BRCA1 and BRCA2 mutations were screened using Sanger sequencing and next-generation sequencing (NGS) methods. Among them, 73 had breast cancer, 43 had ovarian cancer, and the rest were unaffected at the time of screening but had a family history of cancer. The prevalence of pathogenic variants was 34.48% among breast carcinoma patients and 25% among cancer unaffected cases with HBOC family history. This finding is alarming as the incidence of breast carcinoma will rise in the years to come. They have also categorized the spectrum of 34 different pathogenic variants in 20 cases in BRCA1 and 14 cases in BRCA2. The prevalence of BRCA1/2 pathogenic variants in breast cancer cases (31.50%) was lower than ovarian cancer cases (39.53%). In both BRCA1 and BRCA2, most of them were frameshift variants. They have also reported 11 different variants of uncertain significance in 6.3% of the patients. They found a higher number of BRCA1-positive compared to BRCA2 mutations in ovarian cases.
It was a very good paper since the various types of mutations were studied. It is a challenge to differentiate between pathogenic variants from benign non-pathogenic variants among the BRCA1 and BRCA2 mutation carriers. There have been a lot of studies to find out if genetic testing can reduce the incidence of these tumors. BRCA1 and BRCA2 are very large genes. Since the cloning of BRCA1 and BRCA2, more than a thousand mutations have been identified in these genes. In the published literature, there is no compelling evidence to suggest that one genetic test performs better than another. The above paper by Chheda et al. used two different methods to study the mutations. This is one of the limitations of the study. The geographic location of the subjects in the study was not mentioned as the prevalence of mutations may vary across the country. To ensure a full mutation screen, more than one method needs to be used. Harmful mutations in BRCA1/2 genes can produce very high rates of breast and ovarian cancer and increases the risk rates of developing breast cancer by up to 85% and ovarian cancer by up to 54%. Friedman et al. highlighted a constitutional low-level de novo mosaicism, identified by NGS, a pathogenic BRCA1 mutation (c. 1953dupG, 5% of reads) in the DNA extracted from the buccal swab, leukocytes, and normal breast tissues obtained from a triple-negative breast cancer patient, who showed the BRCA1 mutation in tumor tissue (approximately 50% of reads). The mutation was missed in germline DNA by conventional Sanger sequencing. Thus, NGS may be more promising in the identification of mosaicism events that are not always detectable by conventional sequencing methods, due to low mutation frequency.
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Conflicts of interest
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