Predisposition of an Intronic Duplication in CHEK2 Gene in the Cases of Breast Cancer from Balochistan

Baloch, Abdul Hameed; Shuja, Jamila; Bangulzai, Nasrullah; Jan, Mohammad; Sattar, Abdul; Brohi, Sarfaraz Ahmed; Habibullah, Habibullah; Baloch, Dost Muhammad; Ahmad, Jamil

doi:10.31557/APJCP.2025.26.11.3975

Predisposition of an Intronic Duplication in CHEK2 Gene in the Cases of Breast Cancer from Balochistan

Document Type : Research Articles

Authors

¹ Department of Department of Biotechnology and Bioinformatics, Lasbela University of Agriculture, Water and Marine Sciences (LUAWMS), Uthal Balochistan, Pakistan.

² Montreal Neurological Institute, McGill University, Montreal, Canada.

10.31557/APJCP.2025.26.11.3975

Abstract

Objective: After BRCA 1&2, CHEK2 is the most frequently predisposing altered gene causing breast cancer in female. The prime objective of the current study was to analyze germline CHEK2 variants and their association with breast cancer in Balochistani population. Methods: Breast cancer is among the most prevalent cancers worldwide and most common diagnosed cancer in women. Mutations in many proto-oncogenes and tumor suppressor genes lead to the development of cancer. Along with the highly penetrance genes BRCA1 and BRCA2 increase the risk of breast cancer, mutations in other genes including CHEK2, a tumor suppressor gene have also been reported to be associated with breast cancer. In current study CHEK2 gene was analyzed for variation in breast cancer patients and controls of Balochistani population. Sequencing results of the DNA samples of the registered cases of breast cancer in CENAR were analyzed using Chromas software and bioinformatics tools including BLAT and RNAfold web server. Results: An intronic variant c.319+38-43dupA falling 38 nucleotide away at splice donor site of the CHEK2 gene exon 2, in 9% breast cancer cases, was identified which has also been previously reported in non-Hodgkin Lymphoma cases. All the cases with identified variant, were affected with invasive ductal carcinoma. Higher tumor grade (III) was reported in >50% of the patients and > 70% of patients diagnosed with advanced stage of cancer. The RNA prediction results revealed the variant falling in the intronic region may code for miRNA that could play an important role in cancer progression. Conclusion: Our results suggest that the intronic variant identified in breast cancer cases as well as reported previously may act as a cancer marker and causing a splice site disruption or altering the posttranscriptional modification of mRNA encoded by CHEK2 gene.

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