Genetic Mutations in Senegalese Women with Breast Cancer.

OBJECTIVE

This study aimed to understand the effect of nucleotide mutations and microsatellite locus instability on breast cancer in Senegalese women.

METHODS

A total of 120 healthy and cancerous tissue samples were analyzed. After PCR/sequencing analysis, the nucleotide variability of two mitochondrial genes (MTCYB and D-loop) and polymorphisms of two microsatellite loci (BAT-25 and BAT-26) were determined. Additionally, structural and correlation analyses were performed between the clinicopathological features and polymorphisms of the genes studied.

RESULT: Multiple variations in MTCYB and the D-loop were identified with much higher frequencies in cancerous tissues. However, MTCYB appeared more affected than the D-loop during carcinogenesis. Regarding the BAT-25 and BAT-26 loci, breast carcinogenesis was associated with instability of these microsatellite loci, with an MSI-H phenotype in 60.71% of tumors. Furthermore, the number of pears and the histological grade impacted patient survival. In addition, mutations at D-loop sites 150 and 152 and BAT-25 stability negatively impacted patient survival. In contrast, BAT-26 instability conferred the advantage of longer post-operative survival. Molecular variance analysis revealed that the clinical heterogeneity of the tumors was a function of the number of invading lymph nodes.

CONCLUSION

This study highlights the high penetrance of mitochondrial mutations in breast cancer in Senegalese women, as well as the predominant role of BAT-25 marker stability and BAT-26 marker instability in breast carcinogenesis.