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ORIGINAL ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 32-41

Spectrum of germline BRCA mutations in hereditary breast and ovarian cancer syndrome in Indian population: A central reference laboratory experience


Department of Integrated Oncopathology, Metropolis Healthcare Ltd., Mumbai, Maharashtra, India

Correspondence Address:
Kirti Chadha
Unit No. 409 to 416, 4th Floor, Commercial Building A, Kohinoor City, Near Kohinoor Mall, Kirol Road, Kurla-W, Mumbai - 400 070, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_101_19

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Introduction: There is a growing need for BRCA1/BRCA2 mutation frequencies among hereditary breast and ovarian carcinoma (HBOC) cases, specifically determined on the grounds of personal and family history profiles in the Indian population. The current study was intended to identify BRCA1/2 mutation frequency and spectrum in Indian women fulfilling the National Comprehensive Cancer Network criteria. Methods: One hundred and sixty unrelated women were screened for germline variations in BRCA1 and BRCA2 genes by sequencing. The variants were classified as pathogenic or benign on the basis of American College of Medical Genetics (ACMG) guidelines. Results: Of 160 women screened for BRCA mutations, 51 (31.9%) carried a pathogenic variant in BRCA1 (n = 36) or BRCA2 (n = 15) gene. An increased frequency of mutation was seen in women with a personal history of breast or ovarian cancer (34.5%) in comparison to unaffected family members (25%). A spectrum of 34 different pathogenic variants (20 in BRCA1 and 14 in BRCA2) was identified in 51 cases. This included a novel variant c.3683_3684dup in BRCA1 which was categorized as a pathogenic variant. The variant c.68_69delAG in BRCA1 was identified in 12/51 positive cases and appears to be the hotspot mutation in the Indian population. In addition, 11 different missense variants were identified in 10 of the study participants and were categorized as variants of unknown clinical significance (VUS) based on the ACMG guidelines. Of these, three of the variants (c.389A>C in BRCA1 and c.3179G>A and c.10124G>T in BRCA2) were unreported in the published literature. Conclusion: The prevalence of pathogenic variants in the Indian HBOC cohort is high and is similar to other Indian studies. The spectrum of BRCA variants is also diverse, and it is very important to correctly classify them as pathogenic, VUS, or benign. We reinforce the importance of complete BRCA gene screening in the index case, followed by genetic counseling and targeted mutation analysis in other at-risk family members.


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