شناسایی جهش های جدید در اگزون 11 ژنBRCA1 در بیماران مبتلا به سرطان پستان ارثی

Introduction: Breast cancer is the most common malignancy in women worldwide. BRCA1 is a tumor suppressor gene that is involved in DNA-damage repair. One of the significant risk factors of breast cancer is the family history. BRCA1 gene consists of 24 exons that encode a protein with 1863 amino acids. Exon 11 is the largest exons and most of the disease-linked mutations have been found in it. Inherited mutations in the BRCA1 gene are constituted for the major hereditary breast cancer cases. Deficiency in BRCA1 gene was considered to be a high risk in the families with breast cancer. The goal of this study was to evalute mutation in BRCA1 gene in the patients with breast cancer. Methods: In this study, blood samples were collected from 200 breast cancer patients. 40 patients suffer from hereditary breast cancer, after DNA extraction, exon 11 of BRCA1 genes were evaluated by PCR-SSCP technique followed by direct sequencing and the result of the changes was evaluated by in silico analysis. Results: The samples, showing mobility shift on SSCP analysis, were used for direct DNA sequencing, two new missense mutations c.3059C>T (p.Pro1020Leu) and (p.Thr1025Ile) c.3074C>T were detected in the patients with hereditary breast cancer. In silico analysis on protein function revealed that the mutation c.3074C>T effected on protein structure and predicted to be possibly damaging. Conclusion: Screening of the BRCA1 gene mutation can help to manage the treatment of the patients and their families. Therefore, for families exposed to cancer, genetic screening can help family members know if they need tests to look for cancer early, or if they should take steps to reduce their risk.