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Tumor Discovery

ORIGINAL RESEARCH ARTICLE
Haplotype analysis and linkage disequilibrium

of BRCA genes in glioblastoma: Impact on
treatment response

1
2
3
Mohamed K. Khalifa , Amira M. Nageeb , Magdy M. Mohamed ,
2
4
Lobna R. Ezz El Arab , and Menha Swellam *
1 Molecular Pathology Laboratory, Children’s Cancer Hospital, Cairo, Egypt
2 Department of Biochemistry, Biotechnology Research Institute, High Throughput Molecular and
Genetic Laboratory, Central Laboratories Network and the Centers of Excellence, National Research
Centre, Giza, Egypt
3 Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
4 Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Abstract

Glioblastoma (GBM) is an aggressive primary brain tumor prevalent in adults,
characterized as a common malignant neoplasm of the human central nervous
system with the worst survival rate among cancers. Treatment of GBM involves
the addition of the alkylating agent temozolomide (TMZ) to radiotherapy, which
improves overall survival by preventing replication through alkyl group-mediated
DNA cross-linking. Genes related to homologous recombination (HR)-dependent
DNA repair, such as the breast cancer susceptibility genes (BRCA), specifically
*Corresponding author: BRCA1 or BRCA2, contribute to cellular resistance to alkylating agents. We aimed
Menha Swellam to perform a haplotype-based study on the frequencies of BRCA1 mutations in
(menhamswellam@gmail.com) GBM patients compared to healthy individuals and investigate their linkage
Citation: Khalifa MK, Nageeb disequilibrium (LD) with the data population. Blood samples from GBM patients
AM, Mohamed MM, El Arab LRE, (n = 15) and healthy controls (n = 25) were sequenced using the Ion Torrent PGM
Swellam M. Haplotype analysis
and linkage disequilibrium of BRCA platform to identify the BRCA1 mutation. Subsequently, the reported variants
genes in glioblastoma: Impact on were submitted to the LDlink tool for haplotype analysis, and their association
treatment response. Tumor Discov. with treatment response was assessed. Our results revealed that the BRCA1
2024;3(1):1480.
https://doi.org/10.36922/td.1480 haplotype block consisted of seven SNPs, whose frequencies were reported with
strong LD when compared to all available population data. This block was found
Received: August 9, 2023
Accepted: November 30, 2023 to be represented by eight haplotypes. Five of these haplotypes were previously
Published Online: February 15, reported (four haplotypes were commonly reported, and one was rare), while the
2024 remaining three haplotypes were newly reported in this study. The relationship
Copyright: © 2024 Author(s). between newly reported haplotypes and response to treatment revealed that
This is an Open-Access article patients with these haplotypes responded to TMZ either as a complete or partial
distributed under the terms of the
Creative Commons Attribution response. In addition, one haplotype in the heterozygote form was reported in
License, permitting distribution, the control case. In conclusion, haplotype analysis for BRCA genes in GBM cases
and reproduction in any medium, can aid in predicting treatment responses and identifying cancer risk factors in
provided the original work is
properly cited. individuals.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Breast cancer susceptibility genes; Haplotype; Next-generation sequencing;
regard to jurisdictional claims in Sequencing; Breast cancer
published maps and institutional
affiliations.

Volume 3 Issue 1 (2024) 1 https://doi.org/10.36922/td.1480