AccScience Publishing / TD / Volume 3 / Issue 1 / DOI: 10.36922/td.1480
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Haplotype analysis and linkage disequilibrium of BRCA genes in glioblastoma: Impact on treatment response

Mohamed K. Khalifa1 Amira M. Nageeb2 Magdy M. Mohamed3 Lobna R. Ezz El Arab4 Menha Swellam2*
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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
Tumor Discovery 2024, 3(1), 1480
Submitted: 9 August 2023 | Accepted: 30 November 2023 | Published: 15 February 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

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 BRCA1 or BRCA2, contribute to cellular resistance to alkylating agents. We aimed to perform a haplotype-based study on the frequencies of BRCA1 mutations in GBM patients compared to healthy individuals and investigate their linkage disequilibrium (LD) with the data population. Blood samples from GBM patients (n = 15) and healthy controls (n = 25) were sequenced using the Ion Torrent PGM platform to identify the BRCA1 mutation. Subsequently, the reported variants were submitted to the LDlink tool for haplotype analysis, and their association with treatment response was assessed. Our results revealed that the BRCA1 haplotype block consisted of seven SNPs, whose frequencies were reported with strong LD when compared to all available population data. This block was found to be represented by eight haplotypes. Five of these haplotypes were previously reported (four haplotypes were commonly reported, and one was rare), while the remaining three haplotypes were newly reported in this study. The relationship between newly reported haplotypes and response to treatment revealed that patients with these haplotypes responded to TMZ either as a complete or partial response. In addition, one haplotype in the heterozygote form was reported in the control case. In conclusion, haplotype analysis for BRCA genes in GBM cases can aid in predicting treatment responses and identifying cancer risk factors in individuals.

Breast cancer susceptibility genes
Next-generation sequencing
Breast cancer
Science and Technology Development Fund (STDF) through Capacity Building Grant Fund (CBG)
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Conflict of interest
The authors declare that they have no competing interests.
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Tumor Discovery, Electronic ISSN: 2810-9775 Published by AccScience Publishing