Cancer Research, Statistics, and Treatment

: 2020  |  Volume : 3  |  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

Correspondence Address:
Rajesh Singh Laishram
Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur

How to cite this article:
Laishram RS. Study of BRCA mutation variations: Need of the hour.Cancer Res Stat Treat 2020;3:373-374

How to cite this URL:
Laishram RS. Study of BRCA mutation variations: Need of the hour. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Apr 18 ];3:373-374
Available from:

Full Text

Breast cancer is the most commonly diagnosed cancer in women and the second most common cause of death from cancer among women.[1] 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.[2] 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.[2] 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%.[3] Friedman et al.[4] 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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
2Chheda P, Pande S, Dama T, Vinarkar S, Chanekar M, Limaye S, et al. Spectrum of germline BRCA1/2 mutations in hereditary breast and ovarian cancer syndrome in Indian population: A central reference laboratory experience. Cancer Res Stat Treat 2020;3:32-41.
3Toss A, Tomasello C, Razzaboni E, Contu G, Grandi G, Cagnacci A, et al. Hereditary ovarian cancer: Not only BRCA 1 and 2 genes. Biomed Res Int 2015;2015:341723.
4Friedman E, Efrat N, Soussan-Gutman L, Dvir A, Kaplan Y, Ekstein T, et al. Low-level constitutional mosaicism of a de novo BRCA1 gene mutation. Br J Cancer 2015;112:765-8.