Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size