Browsing by Author "Rotimi, Solomon O"

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    Abstract 6346: The chromatin remodeler SMARCA5 selectively shapes nuclear receptor signaling in African American prostate cancer
    (Cancer Res (2025) 85 (8_Supplement_1):, 2025-04-15) Hussain, Shahid; Nayak, Debasis; Wani, Sajad A.; Elhussin, Isra; Freeman, Michael R.; Coss, Christopher C.; Rotimi, Solomon O; Murphy, Adam R.; Yates. Clayton; Campbell, Moray J.
    Motif enrichment in H3K27ac revealed significant differences with Helix-Loop-Helix motifs enriched in RC43N compared to HPr1AR; and STAT motifs enriched in RC43T compared to LNCaP. Similarly, nuclear receptor (NR) motifs were distinct with vitamin D receptor (VDR) and orphan receptors (e.g., RORG) enriched in RC43T compared to LNCaP. Next we up-regulated SMARCA5’s using dCas9-VP64-activator in the same cells and tested the impact on gene expression with RNA-Seq following treatment with the VDR ligand (1, 25(OH)2D3, 100nM). SMARCA5 regulated ∼1200 genes in both RC43T and RC77T, and only ∼200 genes in LNCaP. The SMARCA5-dependent genes in AA PCa cells models were significantly enriched for luminal-differentiation genes. Likewise, in the AA compared to EA PCa models, GSEA analyses revealed enrichment for inflammation responses, and distinct NR signaling, such as progesterone signaling. Likewise LISA analyses revealed enrichment in the SMARCA5-dependent genes in AA PCa for progesterone signaling. Finally, we also identified a subset of miRNA related to differentiation that were uniquely regulated in AA PCa models by 1, 25(OH)2D3 and a significant number were also SMARCA5-dependent. Ongoing studies are addressing the effect of SMARCA5 on chromatin accessibility using ATAC-Seq. Overall, these studies support the concept the epigenome is shaped by genomic ancestry. The epigenomic-regulator SMARCA5 is significantly downregulated in AA PCa and impacts NRs, including VDR signaling. These findings suggest that African ancestry shapes SMARCA5 functions, NR signaling, and tumor outcomes.
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    Tumor-normal sequencing reveals novel TP53 germline and clinically actionable somatic mutations in Nigerian breast cancer patients
    (Cancer Genetics Volumes 300–301, 2026-01) Onyia, Abimbola F.; Lawal, AbdulRazzaq; Ogo, Chidiebere; Nkom, Ebenezer S.; Lasebikan, Nwamaka N.; Ayegbusi, Olaitan T.; De Campos, Opeyemi C.; Rotimi, Oluwakemi A; Oyelade, Jelili O.; Aliyu, Usman M.; Iweala, Emeka E.J.; Rotimi, Solomon O
    Purpose Disparities in the care and management of breast cancer (BC) contribute to poor outcomes and limited access to precision oncology in Nigerian patients. Existing studies on Nigerian patients have largely been conducted abroad, restricting their direct application to local healthcare. This study addresses this gap through a locally led investigation of germline and somatic mutations using tumor-normal paired sequencing. Methods Forty-two female BC patients were recruited from teaching hospitals between January and April 2024. DNA was extracted from blood and matched fresh-frozen tumor tissue. Targeted sequencing of 50 cancer-related genes was performed with the Illumina AmpliSeq Cancer Hotspot Panel and MiSeq platform. Germline and somatic variants were identified through matched normal filtering, with oncogenic significance assessed using the ESCAT/ESMO Tier classification. Visualization was performed in R (v4.4.2) using the maftools package. Results A germline TP53 pathogenic variant, TP53 c.694dupA (p.Ile232Asnfs) was identified in a 35-year-old triple-negative BC patient with recurrent metastatic disease, representing its first report as a germline alteration. Additionally, eighteen oncogenic/likely oncogenic somatic variants were detected, nine of which were actionable (Tier IIII). EGFR amplification was found in 7 % of patients, alongside copy number losses in genes including CDKN2A and KIT. Conclusion This study demonstrates the feasibility of localized tumor-normal sequencing in Nigerian BC patients, revealing actionable variants with clinical relevance. These findings highlight the need to integrate genomic profiling into routine cancer care and establish molecular tumor boards to advance precision oncology in Nigeria.