Mutational and Expression Profile of ZNF217, ZNF750, ZNF703 Zinc Finger Genes in Kenyan Women Diagnosed with Breast Cancer

Background Breast cancer remains a major public health challenge globally and is the leading cancer among women in Kenya. Despite remarkable progress in molecular developments, the genomic and transcriptional features of breast cancer in African populations are still not fully elucidated. While zinc finger proteins (ZNFs) are central regulators of gene expression and have implications for cancer, their involvement in development has not yet been elucidated in breast cancer patients in Kenya. The current study profiled the mutational characteristics of ZNF217, ZNF703, and ZNF750, compared their expression patterns in tumor and matched adjacent non-tumor tissues, and analyzed associations with clinical aspects. Methods Whole-exome and RNA sequencing analyses were performed on 23 pair-matched tumor-normal samples. The somatic mutations were extracted using MuTect2, following standard preprocessing and annotation steps, and identified at protein regions. Gene expression was quantified using STAR, featureCounts, and DESeq2. Paired statistical methods were used to assess differential expression between tumor and matched normal tissues using false discovery rate correction. Associations between gene expression and clinical variables were evaluated using correlation analysis and multivariable regression models. Results ZNF217 (170 mutations) and ZNF750 (164 mutations) had high mutation load consisting mostly of single-nucleotide variants, and that of ZNF703 (24 mutations) was reported less frequently. However, mutations occurred across protein sequences in general, with limited domain enrichment; a recurrent ZNF217 mutation overlapped with a zinc finger domain. Comparison with TCGA data showed a much lower mutation frequency, indicating population specificity. Tumors were notable for upregulation of all three genes relative to normal tissues (ZNF217: p = 0.00068; ZNF703: p = 0.00475; ZNF750: p = 0.00366). In most samples, tumor expression exceeded matched normal expression, and a small number of samples showed the opposite expression trend, indicating molecular heterogeneity. PC1 and PC2 accounted for 75.41% and 13.41% of the total variance for tumor and normal samples, respectively, according to principal component analysis. Clinical results were limited; however, ZNF703 expression was associated with body mass index (β = 0.194, p = 0.025), and ZNF750 expression was elevated in estrogen receptor–positive tumors (β = 1.050, p = 0.005). Conclusions These results show that ZNF217, ZNF703, and ZNF750 are functionally both GM (genetically and transcriptionally dysregulated) in breast cancer and play different functions in tumor biology in breast cancer. Findings of this study underscore the necessity of community-derived genomic research and offer novel perspectives on zinc finger gene expression in overlooked groups.