Back to Journals » The Application of Clinical Genetics » Volume 11

Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients

Authors Shah ND, Shah PS, Panchal YY, Katudia KH, Khatri NB, Ray HSP, Bhatiya UR, Shah SC, Shah BS, Rao MV

Received 3 November 2017

Accepted for publication 12 February 2018

Published 9 May 2018 Volume 2018:11 Pages 59—67


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer

Nidhi D Shah,1 Parth S Shah,2 Yash Y Panchal,3 Kalpesh H Katudia,3 Nikunj B Khatri,3 Hari Shankar P Ray,3 Upti R Bhatiya,3 Sandip C Shah,3 Bhavini S Shah,1 Mandava V Rao4

1Department of Pediatrics, Nassau University Medical Center, New York City, NY, USA; 2Department of Medicine, Lahey Hospital and Medical Center, Boston, MA, USA; 3Supratech Micropath Laboratory and Research Institute, Ahmedabad, Gujarat, India; 4School of Sciences, Gujarat University, Ahmedabad, Gujarat, India

Background: Germline mutations BRCA1 and BRCA2 contribute almost equally in the causation of breast cancer (BC). The type of mutations in the Indian population that cause this condition is largely unknown.
Purpose: In this cohort, 79 randomized BC patients were screened for various types of BRCA1 and BRCA2 mutations including frameshift, nonsense, missense, in-frame and splice site types.
Materials and methods: The purified extracted DNA of each referral patient was subjected to Sanger gene sequencing using Codon Code Analyzer and Mutation Surveyor and next-generation sequencing (NGS) methods with Ion torrent software, after appropriate care.
Results: The data revealed that 35 cases were positive for BRCA1 or BRCA2 (35/79: 44.3%). BRCA2 mutations were higher (52.4%) than BRCA1 mutations (47.6%). Five novel mutations detected in this study were p.pro163 frameshift, p.asn997 frameshift, p.ser148 frameshift and two splice site single-nucleotide polymorphisms (SNPs). Additionally, four nonsense and one in-frame deletion were identified, which all seemed to be pathogenic. Polymorphic SNPs contributed the highest percentage of mutations (72/82: 87.8%) and contributed to pathogenic, likely pathogenic, likely benign, benign and variant of unknown significance (VUS). Young age groups (20–60 years) had a high frequency of germline mutations (62/82;75.6%) in the Indian population.
Conclusion: This study suggested that polymorphic SNPs contributed a high percentage of mutations along with five novel types. Younger age groups are prone to having BC with a higher mutational rate. Furthermore, the SNPs detected in exons 10, 11 and 16 of BRCA1 and BRCA2 were higher than those in other exons 2, 3 and 9 polymorphic sites in two germline genes. These may be contributory for BC although missense types are known to be susceptible for cancer depending on the type of amino acid replaced in the protein and associated with pathologic events. Accordingly, appropriate counseling and treatment may be suggested.

Keywords: breast cancer, BRCA1 and BRCA2 gene mutations, polymorphic SNPs, novel types, age, NGS, Sanger gene sequencer

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]