BIOCHEMICAL PROTRATING OF BRCA1 AS AN ONCOGENIC SWITCH IN BREAST INVASIVE CARCINOMA
DOI:
https://doi.org/10.32350/cto.61.02Keywords:
BRCA1, Breast Invasive Carcinoma, DNA damage checkpoints, cell-cycle arrest, proliferation and drug sensitivityAbstract
Breast invasive carcinoma is worldwide worse women malignancy with poor prognosis due to late diagnosis and lack of awareness. BRCA1 has central role in growth suppression, cell-cycle arrest and apoptosis in adverse carcinogenic situations. There is an inevitable need to re-analyze BRCA1 regulatory behavior in multiple breast malignancy parameters for advancing therapeutic regimen. Due to huge bulk of molecular data regarding BRCA1 role in breast carcinoma we design rational in silico pipeline from data generation to analysis. Firstly we used GeneCards: The Human Gene Database of GeneCardsSuite for enrichment analysis, cBioPortal for Cancer Genomic platform for regulatory analysis, UALCAN database for expression analysis, REPAIRtoire database for determining involvement of BRCA1 in repairing pathways and finally Cancer Cell Lines Encyclopedia and the Genomics of Drug Sensitivity in Cancer projects (CCLE GDSC) toolkit for drug sensitivity analysis. Our study reveals BRCA1 insufficient expression with huge number of mutations in IDC that leads to non-functional protein synthesis. BRCA1 majority of mutations are presented in exon 8-11 that becomes unable to interact with RB1, RAD50, RAD51, MRE11, NBS1 and PALB1 damage sensing/repairing partners. BRCA1 promoter hyper methylation also reduces BRCA1 regulation which is alarming factor for damage repairing apparatus. BRCA1-repairing pathways association also highlights its core significance in tumor protective system. BRCA1 regulation also has ideal supportive role in anti-cancer drug performance. On the basis of these insilico outcomes in future there is an urgent need to design rational strategies for activation of BRCA1 mutation reversal pathways, inhibition of methylation pathways towards BRCA1, construct BRCA1-drug correlome map for ideal prognosis and identification of alternative options other than BRCA1.
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Copyright (c) 2026 Zafar Abbas Shah, Shumaila Noreen, Faisal Nouroz
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