Mutational and Expression Profile of ZNF217, ZNF750, ZNF703 Zinc Finger Genes in Kenya Women diagnosed with Breast Cancer
Abstract
Objectives
To 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.
Methods
Whole-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 ≥ 1.5, p < 0.05). Two-sample t-tests (mutations) and ANOVA (expression) evaluated relationships with HER2 status and clinical stage.
Results
A 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→T and A→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).
Conclusions
Kenyan 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 trio’s 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.
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