Programme: BIochemistry

Permanent URI for this collectionhttp://itsupport.cu.edu.ng:4000/handle/123456789/28779

Here you will find works strictly related to Biochemistry

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Author: search.filters.author.Rotimi, Oluwakemi A.Has files: Yes

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    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.
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    Advancements in Biomarkers of Prostate Cancer: A Review
    (Technology in Cancer Research & Treatment Volume 23, 2024) Agbetuyi-Tayo, Praise; Gbadebo, Mary; Rotimi, Oluwakemi A.; Rotimi, SolomonO.
    Prostate cancer (PCa) is one of the most prevalent and deadly cancers among men, particularly affecting men of African descent and contributing significantly to cancer-related morbidity and mortality worldwide. The disease varies widely, from slow-developing forms to highly aggressive or potentially fatal variants. Accurate risk stratification is crucial for making therapeutic decisions and designing adequate clinical trials. This review assesses a broad spectrum of diagnostic and prognostic biomarkers, many of which are incorporated into clinical guidelines, including the Prostate Health Index (PHI), 4Kscore, STHLM3, PCA3, SelectMDx, ExoDx Prostate Intelliscore (EPI), and MiPS. It also highlights emerging biomarkers with preclinical support, such as urinary non-coding RNAs and DNA methylation patterns. Additionally, the review explores the role of tumor-associated microbiota in PCa, offering new insights into its potential contributions to disease understanding. By examining the latest advancements in PCa biomarkers, this review enhances understanding their roles in disease management
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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) 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.
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    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.
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    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.
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    Abstract 3455: Prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a Western Nigerian population
    (Volume 84, Issue 6_Supplement POSTER PRESENTATIONS - PROFFERED ABSTRACTS, 2024-03-15) Vachon, Celine M; Allmer, Cristine; Moonen, Danelle; Norman, Aaron; Cook, Joselle; Slager, Susan; Rotimi, Oluwakemi A.; De Campos, Opeyemi C; Dokumu, Titilope M.; Murray, David; Kumar, Shaji; Brown, Elizabeth; Baughnm, Linda B; Rotimi, Solomon
    Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by plasma cell production of monoclonal (M) protein and is a requisite precursor to multiple myeloma (MM). African American (AA) individuals have a two-fold higher incidence of MGUS and MM compared to White individuals. However, data are limited on individuals from Africa, especially using sensitive MGUS detection methods. We examined the prevalence of MGUS in a sample of the general population in Nigeria. Individuals aged 40 and over (n=343) were recruited through health promotion events in Ado-Odo Ota Local Government Area of Ogun State, Nigeria, and provided informed consent, a blood sample, and a short questionnaire. Serum was screened at Mayo Clinic for heavy chain (HC)-MGUS using the matrix-assisted laser desorption/ionization-time of flight (Mass-Fix) assay, which has high sensitivity for detection of M-proteins; serum free light chains (FLC) were also measured. FLC was abnormal if the kappa (>0.26 mg/dL) or lambda (>0.33 mg/dL) light chain (LC) was elevated and FLC ratio (kappa/lambda) was outside the reference range (0.26-3.10). LC-MGUS was defined as an abnormal FLC in the absence of a HC. Age- and sex adjusted prevalence rates were directly standardized to 2010 United States (US) population for comparison to published studies. Logistic regression was used to examine the association of age, sex, and BMI with HC-MGUS. The mean age of participants was 55 years (SD=10.9), and 74.6% were female. Of these, 216 (63%) had both parents from the Yoruba tribe, 89 (26%) from the Igbo tribe and 38 (11%) from other tribes. Overall, 33 participants (9.6%) had HC-MGUS, with 8 (2.3%) having an M protein above 0.2 g/dL; 6 (1.7%) had LC-MGUS. HC-MGUS was predominantly IgG isotype (48.5%), followed by IgA (27.3%), biclonal (15.2%) and IgM (9.0%). Prevalence of HC-MGUS was 8.3% for ages 40-49, 7.7% ages 50-69 and 22% ages 70 and above. Standardized to the US population, age and sex adjusted MGUS prevalence ages 50 and older was 17.3% (95% CI: 9.8%-24.9%) and HC-MGUS was 14.7% (95% CI: 7.7% 21.8%), similar to previously published rates of HC-MGUS using Mass-Fix screening of AA individuals (16.5%, 95% CI: 12.2%-20.8%) (PMID: 35316833). In models that included age, sex and BMI, older age was positively associated with HC-MGUS (OR=3.1, 95% CI: 1.1-8.7 for ages 70+ compared to <50), while female sex (OR=0.53, 95% CI: 0.24-1.2) and overweight/obesity (OR=0.34, 95% CI: 0.16-0.75 for BMI > 25 vs. <25) were inversely associated with HC-MGUS. We observed similar prevalence of HC MGUS at ages 50 and above among Western Nigerian and AA populations when screened using mass-spectrometry. Older age was positively associated with HC MGUS while overweight and obesity were inversely associated. Studies of MGUS in indigenous African populations may provide insight to unique cancer risk factors compared to other populations.