Identification of Novel Functional Single Nucleotide Polymorphisms in the Brca1 Gene of Breast Cancer Patients Publisher



Miresmaeili M¹ ; Nabiafjadi M² ; Lagzian A³ ; Fathi Z⁴ ; Yazdanpour M⁵ ; Zalpoor H⁶ ; Yaghoubzadmaleki M⁹ ; Moeini AM¹⁰ ; Arman I¹¹
Source: Iranian Journal of Science Published:2024

Abstract

Breast cancer is the most common cancer in women, making for one-third of all malignancies in females. Between 40 and 45 percent of instances of hereditary breast cancer are caused by mutations in the breast and ovarian cancer susceptibility gene 1 (BRCA1). Breast cancer risk is raised by mutations in its Really Interesting New Gene (RING) and BRCA1 C-Terminal (BRCT) domains. Thus, the goal of this study was to identify new mutations in the BRCA1 gene's RING and BRCT domains. To examine BRCA1 mutation spectra, 107 patients were chosen who had a documented family history of ovarian or breast cancer. Direct DNA sequencing and single-stranded conformational polymorphism (PCR-SSCP), both based on the polymerase chain reaction, were used to screen for mutations in the RING and BRCT domains of the BRCA1 gene. In-silico analysis was used for the in-vitro research outcome. The study's findings indicated that the population carries several BRCA1 sequence variations, including C.55C > A, C.36A > T, C.60A > T, C.199G > C, C.164A > T, C.251A > G, C.4996T > G, C.5032A > T, C.5041A > G, and C.5291T > A. The Breast Cancer Information Core (BIC) searched and examined the mutations. Every mutation was a new mutation. Additionally, a bioinformatics investigation revealed that several variations had an impact on the pathogenicity and stability of the protein. After calculating the relative risk (RR) of research linked to danger, it was found that there was a strong correlation (RR = 1) between the newly discovered genetic mutations and an elevated risk of breast cancer. Our research emphasizes the value of mutation screening in cases of familial ovarian or breast cancer, as well as the possible ramifications of these results for genetic counseling and cancer prevention. © The Author(s), under exclusive licence to Shiraz University 2024.