Department of Biochemistry
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Item Abstract 999: Spectrum of germline BRCA1/2 gene mutations in Nigerian breast cancer patients(Cancer Res (2025) 85 (8_Supplement_1):, 2025-04-21) Onyia, Abimbola F.; Jibrin, Paul; Olatunji-Agunbiade, Temitope; Oyekan, Ademola; Lawal, AbdulRazzaq; Alabi, Adewumi; Sowunmi, Anthonia C.; Aje, Eben A.; Ogunniyi, Oluwabusayo B.; Nkom, Ebenezer S.; De Campos, Opeyemi C.; Rotimi, Oluwakemi A.; Oyelade, Jelili O.; Rotimi, Solomon O.Breast cancer (BC) is the leading cause of cancer-related deaths in Nigerian women, with triple-negative breast cancer (TNBC) being the most prevalent. The TNBC subtype is characterized by mutations in BRCA1 and BRCA2 genes, and germline pathogenic carriers of these mutations have an increased risk for BC. Despite these challenges, the prevalence and spectrum of BRCA1/2 pathogenic variants in the Nigerian population differ, and there is a margin in the local capacity to characterize these variations. Therefore, this study aimed to identify and characterize germline variations in BRCA 1/2 genes in Nigerian BC patients and healthy aged-matched controls to understand the genetic risk profiles of BC in this population. Forty-five BC patients were recruited across four major hospitals in Nigeria and aged-matched with 51 healthy female controls. DNA was extracted from blood samples, followed by targeted sequencing of BRCA 1/2 intronic and exonic regions using the Ampliseq for BRCA panel and the Illumina Miseq Platform. Variant calling was performed, and the clinical significance of identified variants was evaluated on the ClinVar and BRCA exchange databases. Variants of unknown significance (VUS) were assessed using known in silico prediction software, and haplotype analysis was carried out using the Haploview 4.2 software. Pathogenic variants were identified in 6.7% of cases, all exclusive to BC patients. These variants included two BRCA1 variants (3: c.133_134delAA (p.Lys45fs) and c.5324T>A (21: p.Met1775Lys), and one BRCA 2 variant (22: c.8817_8820del (p.Lys2939fs) all found in patients with the TNBC subtype. Additionally, 97 benign or likely benign BRCA1/2 variants were found in both BC and control groups, with notable variants such as the rs799917 identified as a surrogate indicator of ancestry. Eighteen VUS were identified, with four predicted to be damaging by three in silico prediction software. The results of haplotype analysis identified distinct BC haplotypes in Nigerian BC patients. The identification of BRCA1/2 pathogenic variants in Nigerian BC patients, especially those with TNBC, suggests a potential for targeted therapies, such as PARP inhibitors, to improve treatment outcomes in this population. This further highlights the need for increased population-specific screening and the integration of genetic screening into BC management strategies, which could facilitate early detection, personalized treatment plans, and genetic counseling for Nigerian BC patients.Item Tumor-normal sequencing reveals novel TP53 germline and clinically actionable somatic mutations in Nigerian breast cancer patients(Cancer Genetics Volumes 300–301, 2026) Onyia, Abimbola F.; Lawal, AbdulRazzaq; Ogo, Chidiebere; Nkom, Ebenezer S.; Lasebikan, Oluwakemi A.; 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.Item INVESTIGATION OF THE ASSOCIATION OF CYSTATHIONINE GAMMA-LYASE (CTH) AND VITAMIN D-BINDING PROTEIN (GC) GENES POLYMORPHISMS WITH PREECLAMPSIA IN SOME PREGNANT WOMEN ATTENDING PRENATAL CARE AT A GENERAL HOSPITAL IN LAGOS NIGERIA(Science World Journal Vol. 20, 2025) Igbalaye, Jimoh O.; Wusu, Adedoja D.; Oyedapo, Abiola F.; Ajape, Azeezat O.; Shakunle, Adebusola; Fatai, Azeez A.; Rotimi, Solomon O.Preeclampsia is associated with high maternal and foetal morbidity and mortality. Studies have demonstrated that polymorphisms in the genes that regulate vascular dynamics may play vital roles in the development of chronic hypertension and preeclampsia. This study aimed to evaluate the relationship between polymorphisms in the rs1021737G>T of the cystathionine gamma-lyase (CTH), and rs7041G>T & rs4588C>A of the vitamin D-binding protein (GC) genes and the risk of preeclampsia in pregnant Nigerian women. A case-control study was conducted. Blood samples collected from 73 patients (8 cases and 65 controls) were used for DNA genotyping, while 101 patient blood samples (15 cases and 86 controls) were utilised for the plasma H2S levels evaluation. The examined polymorphisms were determined using the PCR-RFLP method. Unconditional logistic regression analysis reveals no statistically significant difference among the odds ratio (OR) and 95% confidence interval (CI) of the genotypes and alleles for the rs1021737G>T of the CTH gene, and rs7041G>T & rs4588C>A of the GC gene. Furthermore, there were no relationships between studied polymorphisms and selected clinical parameters. The preeclamptic pregnant women showed no statistically significant difference in plasma H2S level (32.8715.16 vs. 56.2933.34 μM, p = 0.055) as compared with the control group. This study suggests that examined polymorphisms in the CTH and GC genes are not associated with preeclampsia development in pregnant Nigerian women. Further studies with large sample sizes are needed to confirm these findings.Item Vitamin D Receptor Polymorphism and its Clinical Relevance in Prostate and Colon Cancer Patients: A Study in a Tertiary Institution in Nigeria(Journal of Radiation and Cancer Research, 2025-10) Aje, Eben A.; Sowunmi, Anthonia; Alabi, Adewumi; Agbakwuru, Chidi; Oshikanlu, Bukola; Rotimi, Solomon O.; Bashir, Maryam; Rotimi, Oluwakemi; Habeebu, Muhammad; Bolanle, AdegboyegaIntroduction: This study examines the clinical relevance of Vitamin D receptor (VDR) polymorphisms in prostate and colon cancer patients at NSIA LUTH Cancer Centre, Lagos, Nigeria. With limited African data on Vitamin D’s genetic role in cancer, we investigate its association with cancer susceptibility, grade, and stage. Methods: A total of 142 cases and controls were recruited, including newly diagnosed and treated prostate and colon cancer patients. The study received ethical approval from the Lagos University Teaching Hospital Ethical Committee and was self‑funded. Serum Vitamin D levels were assessed using ELISA, while VDR polymorphisms (Fok1, BsmI, TaqI, and ApaI) were analyzed via restriction fragment length polymorphism‑polymerase chain reaction. Results: The study found a significant association between Vitamin D deficiency and both prostate and colon cancers. Serum Vitamin D levels declined with increasing cancer grade and stage. In colon cancer, Vitamin D levels dropped from 43.8 ng/ml in stage I to 34.9 ng/ml in stage IV. In prostate cancer, a sharp decline was observed from 62.6 ng/ml in stage I to 29.8 ng/ml in stage IV. Patients with low Vitamin D levels had higher cancer risk (odds ratio [OR]: 3.1 for colon cancer; OR: 2.2 for prostate cancer). VDR polymorphism analysis revealed significant associations between cancer cases and specific genotypes: Fok1 (FF), BsmI (Bb), TaqI (tt), and ApaI (aa). Patients with these polymorphisms had lower Vitamin D levels, suggesting a genetic predisposition to cancer progression. Conclusion: This study highlights the impact of Vitamin D deficiency and VDR polymorphisms on prostate and colon cancer biology. The findings emphasize their potential roles in disease progression and suggest further research into Vitamin D supplementation as a protective measure in cancer patientsItem Updates onSPOPGeneMutationsinProstateCancerand Computational InsightsFromTCGAcBioPortalDatabase(Wiley Scientifica Volume 2025, 2025) Zakari, Suleiman; Rotimi, Solomon O.; Bholah, Chandra Tatsha; Ogunlana, OlubankeO.Speckle-type poxvirusandzinc*ngerprotein(SPOP)hasemergedasakeyfocusinprostatecancerresearchduetoitscriticalrole in regulatingtheandrogenreceptor(AR)signalingpathway./isreviewaimstocomprehensivelysummarizecurrentknowledge on SPOPgenemutationsinprostatecancer,emphasizingtheirimportanceindiseasecharacterizationandidenti*cationof therapeutic targets.Asystematicliteraturesearchwasconductedacrossmultipledatabases,includingPubMed,WebofScience, Scopus, andGoogleScholar.Inaddition,thisstudyusescomputationalapproachesanddatafromtheTCGAcBioPortaldatabase to explorethelandscapeofSPOPmutationsinprostatecancer.Afterscreening682articlesandfollowingsystematicselection steps, 56high-qualityarticleswereincluded.ComputationalanalysisofTCGAcBioPortaldatarevealedaSPOPmutation prevalence of5%-6%,alongwithsigni*cantalterationsinARsignalingandepigeneticregulation.SPOPmutationsdisrupt substrate recognition,leadingtodysregulationofdownstreampathwayssuchasARsignalingandchromatinremodeling. Notably, SPOP-mutantprostatecancersaremutuallyexclusivewithTMPRSS2-ERGfusionsandenrichedforWntpathway alterations. PatientswithSPOPmutationsdemonstrateprolongedresponsestoandrogendeprivationtherapy(ADT),although concurrent mutationsinTP53orDNArepairgenesnegativelyimpactoutcomes.Whiletheirprognosticsigni*cancecontinuesto evolve, theirimpactontheARpathwayhighlightstheirpotentialastherapeutictargets./eclinicalimplicationsofSPOP mutations aresubstantial,astheyarelinkedtovariationsintreatmentresponseanddiseaseprogression,thusservingasvaluable biomarkers forriskstrati*cationandprognosis.Item Screening of Germline BRCA1 and BRCA2 Variants in Nigerian Breast Cancer Patients(Technology in Cancer Research & Treatment Volume 24, 2025) Onyia, Abimbola F.; Jibrin, Paul; Olatunji-Agunbiade, Temitope; Oyekan, Ademola; Lawal, AbdulRazzaq; Alabi, Adewumi; Sowunmi, Anthonia C.; Aje, Eben A.; Ogunniyi, Oluwabusayo B; Nkom, Ebenezer S.; De Campos, Opeyemi C.; Rotimi, Oluwakemi A.; Oyelade, Jelili O.; Rotimi, Solomon O.Background: Breast cancer remains a leading cause of mortality among Nigerian women, with triple-negative breast cancer (TNBC) being particularly prevalent. Variations in BRCA1 and BRCA2 genes remain key risk factors for this disease. However, there are gaps in the frequency and spectrum of these variants in Nigerian populations, as well as a dearth in the local capacity to characterize these variations. Objective: This study aimed at identifying and characterizing the germline variations in BRCA1/2 in Nigerian breast cancer patients and healthy age-matched controls to understand the genetic risk profile of breast cancer in this population. Methods: A prospective case-control study was conducted involving 45 breast cancer patients and 51 controls recruited from four major hospitals. DNA was extracted from blood samples, followed by targeted sequencing of BRCA1/2 exonic and intronic regions using the Ampliseq BRCA panel and Illumina MiSeq platform. Variant calling was performed, clinical significance was evaluated on ClinVar and BRCA Exchange databases, and haplotype analysis was performed using NIH LDlink and Haploview 4.2 software. Results: Pathogenic BRCA1/2 variants were identified in 6.7% of breast cancer patients, all with TNBC and a family history of cancer. Two pathogenic BRCA1 variants were detected: a frameshift deletion BRCA1 c.133_134delAA (p.Lys45 fs) (rs397508857) and a missense variant BRCA1 c.5324T >A (p.Met1775Arg) (rs41293463). A BRCA2 frameshift deletion BRCA2 c.8817_8820del (p.Lys2939 fs) (rs397508010) was also identified. These variants were absent in controls. Haplotype analysis revealed distinct BRCA1 and BRCA2 haplotypes in the breast cancer group. Conclusion: This study identifies key BRCA1/2 pathogenic variants and unique haplotypes in Nigerian breast cancer patients, highlighting the need for population-specific genetic screening. Integrating genetic testing into breast cancer management strategies could facilitate early detection, personalized treatment planning, and genetic counseling in Nigeria.Item Abstract 999: Spectrum of germline BRCA1/2 gene mutations in Nigerian breast cancer patients(Cancer Res (2025) 85 (8_Supplement_1), 2025) Onyia, Abimbola F; Jibrin, Paul; Olatunji-Agunbiade, Temitope; Oyekan, Ademola; Lawal, AbdulRazzaq; Alabi, Adewumi; Sowunm, Anthonia C.; Aje, Eben A.; Ogunniyi, Oluwabusayo B.; Nkom, Ebenezer S.; De Campos, Opeyemi C; Rotimi, Oluwakemi A.; Oyelade, Jelili O.; Rotimi, Solomon O.Breast cancer (BC) is the leading cause of cancer-related deaths in Nigerian women, with triple-negative breast cancer (TNBC) being the most prevalent. The TNBC subtype is characterized by mutations in BRCA1 and BRCA2 genes, and germline pathogenic carriers of these mutations have an increased risk for BC. Despite these challenges, the prevalence and spectrum of BRCA1/2 pathogenic variants in the Nigerian population differ, and there is a margin in the local capacity to characterize these variations. Therefore, this study aimed to identify and characterize germline variations in BRCA 1/2 genes in Nigerian BC patients and healthy aged-matched controls to understand the genetic risk profiles of BC in this population. Forty-five BC patients were recruited across four major hospitals in Nigeria and aged-matched with 51 healthy female controls. DNA was extracted from blood samples, followed by targeted sequencing of BRCA 1/2 intronic and exonic regions using the Ampliseq for BRCA panel and the Illumina Miseq Platform. Variant calling was performed, and the clinical significance of identified variants was evaluated on the ClinVar and BRCA exchange databases. Variants of unknown significance (VUS) were assessed using known in silico prediction software, and haplotype analysis was carried out using the Haploview 4.2 software. Pathogenic variants were identified in 6.7% of cases, all exclusive to BC patients. These variants included two BRCA1 variants (3: c.133_134delAA (p.Lys45fs) and c.5324T>A (21: p.Met1775Lys), and one BRCA 2 variant (22: c.8817_8820del (p.Lys2939fs) all found in patients with the TNBC subtype. Additionally, 97 benign or likely benign BRCA1/2 variants were found in both BC and control groups, with notable variants such as the rs799917 identified as a surrogate indicator of ancestry. Eighteen VUS were identified, with four predicted to be damaging by three in silico prediction software. The results of haplotype analysis identified distinct BC haplotypes in Nigerian BC patients. The identification of BRCA1/2 pathogenic variants in Nigerian BC patients, especially those with TNBC, suggests a potential for targeted therapies, such as PARP inhibitors, to improve treatment outcomes in this population. This further highlights the need for increased population-specific screening and the integration of genetic screening into BC management strategies, which could facilitate early detection, personalized treatment plans, and genetic counseling for Nigerian BC patients.Item Integrated single-cell whole genome sequencing and spatial transcriptomics reveal latent intra-tumoral heterogeneity in ovarian cancer(bioRxiv preprint, 2025) Bassiouni, Rania; Jin, Yuxin; Gibbs, Lee D.; Qian, Jing; Rotimi, Solomon O.; Miller, Heather; Webb, Michelle G.; Rajpara, Seeta; Arias-Stella III, Javier; Craig, David W.; Roman, Lynda; Carpten, John D.The mortality rate of ovarian cancer remains disproportionately high compared to its incidence. This is partly due to a high level of intra-tumoral heterogeneity that promotes disease recurrence and treatment failure. In this study, we describe degrees of heterogeneity revealed by single-cell whole genome sequencing and spatial transcriptomics of five epithelial ovarian carcinomas. At the cellular level, we describe pseudo-diploid cells that match the malignant cell population in both somatic variant and copy number patterns. At the clonal and subclonal levels, we describe diversification associated with copy number gains and whole genome doubling. In multi-clonal samples, we infer evolutionary relationships from single cell copy number, loss of heterozygosity analysis, and somatic variant detection, and correlate these with tissue histology and gene expression programs. In one sample, we identify functionally consequential copy number alterations that contribute to molecular diversity, cell proliferation, and inflammation in a minor clone that persisted without major expansion alongside a more complex major clone. In another, we describe a complex evolutionary history including a spontaneous reversion of a driver mutation in a secondary clone, which correlated with a switch in oncogenic expression programs.