Ramatoulaye Niang*, Fatimata Mbaye, Mbacké Sembeme
Objective: Breast cancer is one of the most common diseases affecting women worldwide. However, mortality rates are disproportionately high among Black women, regardless of incidence rates. Although several factors related to age, steroid hormones, breastfeeding, and genetic aberrations have been implicated, the exact mechanism for this disparity remains unclear. The purpose of this study was to investigate the genetic profile of non-coding DNA sequences and determine their potential impact on breast cancer development.
Methods: Tissue samples were obtained from patients at the Joliot-Curie institute in Dakar, Senegal. Using Polymerase Reaction Chain (PCR) and the Sanger method, we sequenced Beta-Fibrinogen (FGB) intron 7 and mitochondrial D-loop region. The nucleotide sequences of both genes were then compared to reference sequences in the MITOMAP, gnomAD, and ensembl databases, and performed analyses using mutation surveyor, CADD, FATHMM-XF, CSCAPE, and CSCAPE-SOMATIC.
Results: We found 77 novel mutations in FGB and D-loop, all of which were heterozygous. The mutational spectrum of the D-loop was transition dominant, unlike that of FGB intron 7. All mutations were tolerated, with the exception of c.1244+75T>A, which was predicted to be oncogenic by cancer-specific software. Our results also indicated a strong association between the mutations in both of the genes.
Conclusion: Thus, further investigations of non-coding areas of DNA may contribute to a better understanding of the development and progression of breast cancer and lead to more effective patient management.