Detection of Large Deletions and Duplications in Moderate Risk Breast Cancer Susceptibility Genes in Breast Cancer Patients Negative for the BRCA1 and BRCA2 Mutations

Introduction. Breast cancer is the most frequently diagnosed malignancy among woman in Latvia. Approximately 40% of all hereditary breast cancer cases can be explained due to the point mutations in the BRCA1 and BRCA2 genes. It is estimated that more than 10% of breast cancer predisposing mutations are large genomic rearrangements such as large deletions and duplications. Aim of the study. The aim of the study was to determine a large deletions, or duplications in the moderate risk breast cancer susceptibility genes in breast cancer patients negative for the point mutations in the BRCA1 and BRCA2 genes. Materials and methods. Study group consisted of 23 breast cancer patients negative for the 4153delA, 5382insC and 873delG, 886delTG mutations in the BRCA1 and BRCA2 genes, respectively. Multiplex ligation-dependent probe amplification was performed for the detection of large genomic deletions and duplications. Results. Large genomic deletions were detected in the two cases. In one case was determined a large genomic deletion in the CHEK2 gene spanning exons 9 and 10. In the second case exons 2 and 5 in the CHEK2 gene and exons 29 and 46 in the ATM gene were deleted. Conclusions. Large genomic deletions in the moderate risk breast cancer susceptibility genes can be found in Latvia. For the first time, a large genomic CHEK2 gene deletion spanning exons 9 and 10 has been detected in Latvia.