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

ObjectivesTo characterize the somatic mutational spectrum and transcriptomic expression of the zinc-finger genes ZNF217, ZNF703, and ZNF750 in Kenyan women with breast cancer, and to explore their associations with clinicopathologic features. MethodsWhole-exome sequencing and RNA-sequencing were performed on paired tumor and adjacent normal tissues from 23 consented patients treated at two Kenyan referral hospitals. Variants were called with Mutect2 using a study-specific panel of normal; functional consequences were annotated with VEP. After featureCounts quantification, differential expression was analyzed in DESeq2 (fold-change [&ge;] 1.5, p < 0.05). Two-sample t-tests (mutations) and ANOVA (expression) evaluated relationships with HER2 status and clinical stage. ResultsA total of 358 somatic mutations were detected: 170 in ZNF217, 24 in ZNF703 and 164 in ZNF750. Single-nucleotide substitutions (319 SNPs) dominated, with C[-&gt;]T and A[-&gt;]G changes most common; 27 deletions and 2 insertions were also observed. Frameshift events in ZNF217 and ZNF703 introduced premature stop codons predicted to truncate protein function. All three genes were significantly up-regulated in tumors versus normal (ZNF217 p = 0.0004), with the greatest expression in HER2-positive tumors and in stages 2-3 disease. Mutation burden for each gene did not differ by HER2 status (p > 0.56) or by stage (p > 0.32). ConclusionsKenyan breast tumors harbor frequent, functionally relevant mutations and marked over-expression of ZNF217, ZNF703, and ZNF750. These alterations, especially the pronounced up-regulation of ZNF217, highlight the trios potential as diagnostic or prognostic biomarkers and warrant larger studies to validate their clinical utility and suitability as therapeutic targets in sub-Saharan African populations.