EPrints - Publications Repository

Ahmad, Hilal and Ali, Asif and Ali, Roshan and Khalil, Ali Talha and Khan, Ishaq and Khan, Mah Muneer and Alorini, Mohammed (2024) Preliminary insights on the mutational spectrum of BRCA1 and BRCA2 genes in Pakhtun ethnicity breast cancer patients from Khyber Pakhtunkhwa (KP), Pakistan. Neoplasia, 51: 100989. ISSN 1522-8002

AI Summary:

The study aimed to identify novel pathogenic and recurrent mutations in BRCA1 and BRCA2 genes in Pakhtun population from Khyber Pakhtunkhwa. The study found unique BRCA1 and BRCA2 mutations in the studied population.

AI Topics:

The following topics are generate through an AI service. Clicking on them will take you to a search result page with related items.

Abstract

Gene mutations are a source of genetic instability which fuels the progression of cancer. Mutations in BRCA1 and BRCA2 are considered as major drivers in the progression of breast cancer and their detection indispensable for devising therapeutic and management approaches. The current study aims to identify novel pathogenic and recurrent mutations in BRCA1 and BRCA2 in Pakhtun population from the Khyber Pakhtunkhwa. To determine the BRCA1 and BRCA2 pathogenic mutation prevalence in Pakhtun population from KP, whole exome sequencing of 19 patients along with 6 normal FFPE embedded blocks were performed. The pathogenicity of the mutations were determined and they were further correlated with different hormonal, sociogenetic and clinicopathological features. We obtained a total of 10 mutations (5 somatic and 5 germline) in BRCA1 while 27 mutations (24 somatic and 3 germline) for BRCA2. Five and seventeen pathogenic or deleterious mutations were identified in BRCA1 and BRCA2 respectively by examining the mutational spectrum through SIFT, PolyPhen-2 and Mutation Taster. Among the SNVs, BRCA1 p.P824L, BRCA2 p. P153Q, p.I180F, p.D559Y, p.G1529R, p.L1576F, p.E2229K were identified as mutations of the interaction sites as predicted by the deep algorithm based ISPRED-SEQ prediction tool. SAAFEQ-SEQ web-based algorithm was used to calculate the changes in free energy and effect of SNVs on protein stability. All SNVs were found to have a destabilizing effect on the protein. ConSurf database was used to determine the evolutionary conservation scores and nature of the mutated residues. Gromacs 4.5 was used for the molecular simulations. Ramachandran plots were generated using procheck server. STRING and GeneMania was used for prediction of the gene interactions. The highest number of mutations (BRCA1 7/10, 70 %) were on exon 9 and (BRCA2, 11/27; 40 %) were on exon 11. 40 % and 60 % of the BRCA2 mutations were associated Grade 2 and Grade 3 tumors respectively. The present study reveals unique BRCA1 and BRCA2 mutations in Pakhtun population. We further suggest sequencing of the large cohorts for further characterizing the pathogenic mutations.

People

Ahmad, Hilal

Organisations

Elsevier

Publisher

Copyright © 2024 The Authors

Copyright holder

Texts

269:277

269:277

324248.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (23MB) |

Information

Title:

Preliminary insights on the mutational spectrum of BRCA1 and BRCA2 genes in Pakhtun ethnicity breast cancer patients from Khyber Pakhtunkhwa (KP), Pakistan

Creators:

Ahmad, Hilal and Ali, Asif and Ali, Roshan and Khalil, Ali Talha and Khan, Ishaq and Khan, Mah Muneer and Alorini, Mohammed

Identification Number:

10.1016/j.neo.2024.100989

Date:

May 2024

Divisions:

College of Medical Veterinary and Life Sciences > School of Cancer Sciences

Publisher:

Elsevier

Additional Information:

This research is funded by the Higher Education Commission Pakistan under the National Research Program for Universities vide Project No. 6820/KPK/NRPU/R&D/HEC/2016.

Library

URI:

https://pub.demo35.eprints-hosting.org/id/eprint/269

Item Type:

Article

Depositing User:

Unnamed user with email ejo1f20@soton.ac.uk

SWORD Depositor:

Users 37347 not found.

Date Deposited:

11 Jun 2025 16:36

Revision: