BAX and BCL-2 Gene Mutation Signature in Benign and Malignant Lesions of the Breast

Author(s):

Ekundina Victor Olukayode*, Awopetu Ayodele Victoria, Oladoye Olawalepelumi Olayinka, Alabi Gloria Oluwagbenro and Iyiola Sina

Background: Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX, a central cell death regulator, is an indispensable gateway to mitochondrial dysfunction and a major pro-apoptotic member of the BCL-2 family proteins that control apoptosis in normal and cancer cells. Dysfunction of apoptosis renders the cancer cell resistant to treatment as well as promotes tumorigenesis. The aim was to study BAX and BCL-2 gene mutations in benign and malignant lesions of the breast.

Materials and methods: A case controlled retrospective study was done with a total of 10 formalin fixed and paraffin wax embedded tissue blocks retrieved from pathology archives, amongst these were 5 benign fibroadenoma and 5 m alignant invasive ductal carcinoma confirmed cases of the breast analyzed using Nucleic acid amplification techniques, the cells was lysed, separated from cellular debris, precipitated, washed with 70% ethanol and eluted, results were presented in SNPs and functional mutation.

Results: This study showed that Bax mutation In Fibroadenoma SNPs observed, 100% transversion, 0% indel and transition. Functional mutation in Fibroadenoma observed, 100% missense, 0% silent and nonsense. In Invasive ductal adenocarcinoma SNPs observed, 58% indel, 29% transversion and 14% transition. Functional mutation in Invasive ductal adenocarcinoma observed, 100% missense and 0% nonsense and silent. BCL-2 mutation in fibroadenoma SNPs observed, 100% transition, 0% indel and 0% transversion. Functional mutation in fibroadenoma observed 67% missense, 0% nonsense and 33% silent. In invasive ductal carcinoma SNPs observed, 30% transversion, 0% insertion and 70% transition. Funcional mutation in invasive ductal carcinoma observed, 40% missense, 60% silent and 0% nonsense. Comparison between BAX and BCL-2 gene in fibroadenoma S NPs observed, 6 0% transition, 4 0% transversion a nd 0% indel. Functional mutation in fibroadenoma observed 8 0% Missense, 20%Silent and 0% Nonsense. In invasive ductal carcinoma SNPs observed, 47% transversion, transition 29% and 24% indel. Funcional mutation in invasive ductal carcinoma observed, 50% missense and 50%Silent and 0% nonsense.

Conclusion: After carrying out this investigation, BAX gene mutation is more defenseless against invasive ductal adenocarcinoma than Fibroadenoma. As a result, mutation in invasive ductal adenocarcinoma in most cases cannot be rectify. In this study, BAX and BCL-2 gene mutation seems to lead to development of breast cancer and affects the disease progression.