A5030507591- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Prostate Cancer Diagnosis and Treatment
- Genomics and Phylogenetic Studies
- Genetic factors in colorectal cancer
- Genetic Associations and Epidemiology
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Forensic and Genetic Research
- Cancer-related gene regulation
- Cancer, Lipids, and Metabolism
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Colorectal Cancer Treatments and Studies
- Genetic diversity and population structure
- Genomics and Rare Diseases
- HIV Research and Treatment
- Hormonal and reproductive studies
- Genomic variations and chromosomal abnormalities
- Immune Cell Function and Interaction
- Forensic Anthropology and Bioarchaeology Studies
- Sexual Differentiation and Disorders
- RNA Research and Splicing
- RNA modifications and cancer
University of Pretoria
2015-2025
The University of Sydney
2016-2025
University of Manchester
2023-2025
Cancer Research UK Manchester Centre
2025
Garvan Institute of Medical Research
2015-2024
University of Limpopo
2013-2024
John Wiley & Sons (United States)
2017-2024
Cancer Research UK Manchester Institute
2023-2024
Stellenbosch University
1996-2023
Sefako Makgatho Health Sciences University
2023
The complete genome sequences of an indigenous hunter-gatherer from Namibia's Kalahari Desert and a Bantu South Africa are presented in this issue, together with protein-coding regions three other groups the Kalahari. Analysis genetic variance what is probably oldest known modern human lineage will contribute to understanding diversity, facilitate inclusion southern Africans medical genomics research projects. Initial observations data include fact that Bushmen seem more different each...
Fusion genes are a major cause of cancer. Their rapid and accurate diagnosis can inform clinical action, but current molecular diagnostic assays restricted in resolution throughput. Here, we show that targeted RNA sequencing (RNAseq) overcome these limitations. First, establish fusion gene detection with RNAseq is both sensitive quantitative by optimising laboratory bioinformatic variables using spike-in standards cell lines. Next, analyse patient cohort improve the overall rate from 63%...
The Tasmanian devil ( Sarcophilus harrisii ) is threatened with extinction because of a contagious cancer known as Devil Facial Tumor Disease. inability to mount an immune response and reject these tumors might be caused by lack genetic diversity within dwindling population. Here we report whole-genome analysis two animals originating from extreme northwest southeast Tasmania, the maximal geographic spread, together genome tumor taken one them. A 3.3-Gb de novo assembly sequence data...
Within-population genetic diversity is greatest within Africa, while between-population directly proportional to geographic distance. The most divergent contemporary human populations include the click-speaking forager peoples of southern broadly defined as Khoesan. Both intra- (Bantu expansion) and inter-continental migration (European-driven colonization) have resulted in complex patterns admixture between ancient geographically isolated Khoesan more recently diverged populations. Using...
Prostate cancer (PCa) is the most common malignant neoplasm among men in many countries. Since precancerous and cancerous tissues show signs of inflammation, chronic bacterial prostatitis has been hypothesized to be a possible etiology. However, establishing causal relationship between microbial inflammation PCa requires comprehensive analysis prostate microbiome. The aim this study was characterize microbiome tissue patients investigate its association with tumour clinical characteristics...
Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages
Abstract Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as grade. To interrogate the evolutionary origins cancer heterogeneity, we analyzed 666 whole genomes. We identified a compendium 223 recurrently mutated driver regions, influencing downstream processes gene expression. validated individual germline variants that predispose tumors to acquire specific...
The docking protein Gab2 is a proto-oncogene product that overexpressed in primary breast cancers. To determine the functional consequences of overexpression, we utilized immortalized human mammary epithelial cell line MCF-10A. In monolayer culture, expression at levels comparable with those detected cancer cells accelerated epidermal growth factor (EGF)-induced cycle progression and was associated increased basal Stat5 tyrosine phosphorylation enhanced and/or more sustained EGF-induced Erk...
STATEMENT: In naming population groups, we think a chief aim is to use terms that the group members themselves, or find familiar and comfortable. The used in this manuscript describe populations are as historically correct possible chosen so not offend any group. Two of authors (DCP REvdR) belong Coloured population, with one (REvdR) having contributed extensively current literature on history people South Africa served Vice-President African Institute Race Relations. According 2001 census...
Mutation detection has, until recently, relied heavily on the use of gel-based methods that can be both time consuming and difficult to design. Nongel-based systems are therefore important increase simplicity improve turn around without compromising assay sensitivity accuracy, especially in diagnostic/clinical setting. In this study, we assessed latest nongel-based methods, namely high-resolution melt (HRM) curve analysis. HRM is a closed-tube method incorporates saturating dye during DNA...
BACKGROUND Compared with White Americans, Black American men are at a significant increased risk of presenting prostate cancer (PCa) and associated mortality, suggesting link to African‐ancestry. However, PCa status within Africa is largely unknown. We address the clinical presentation South African men. METHODS Over 1,000 participants or without have enrolled in Southern Prostate Cancer Study (SAPCS). Using genome‐wide profiling we establish unique population substructure. Adjusting for...
Abstract African-American men are more likely than any other racial group to die from prostate cancer. The contribution of acquired genomic variation this disparity is largely unknown, as Africa lacking. Here, we performed the first tumor-normal paired deep whole-genome sequencing for Africa. A direct study-matched comparison between African- and European-derived, treatment-naïve, high-risk tumors 15 cases allowed further comparative analyses existing data. Excluding a single hypermutated...
The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state which cells persist prior overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling retention cell dormancy. We demonstrate that loss type I IFN occurs proliferating bone. This suppresses tumor immunogenicity therapeutic response promotes activation drive progression....
Abstract Background The German Shepherd Dog (GSD) is one of the most common breeds on earth and has been bred for its utility intelligence. It often first choice police military work, as well protection, disability assistance, search-and-rescue. Yet, GSDs are known to be susceptible a range genetic diseases that can interfere with their training. Such particular concern when they occur later in life, fully trained animals not able continue duties. Findings Here, we provide draft genome...
Abstract The timing of puberty is highly variable and associated with long-term health outcomes. To date, understanding the genetic control based largely on studies in women. Here, we report a multi-trait genome-wide association study for male an effective sample size 205,354 men. We find moderately strong genomic correlation between sexes (rg = 0.68) identify 76 independent signals timing. Implicated mechanisms include unexpected link natural hair colour, possibly reflecting common effects...
Germline testing for prostate cancer is on the increase, with clinical implications risk assessment, treatment, and management. Regardless of family history, NCCN recommends germline patients metastatic, regional, very-high-risk localized, high-risk localized cancer. Although African ancestry a significant factor aggressive cancer, due to lack available data no criteria have been established ethnic minorities.Through deep sequencing, we interrogated 20 most common panel genes in 113 Black...
Alternative CCND1 splicing results in cyclin D1b, which has specialized, protumorigenic functions prostate not shared by the D1a (full length) isoform. Here, frequency, tumor relevance, and mechanisms controlling D1b were challenged.
The oldest contemporary human mitochondrial lineages arose in Africa. earliest divergent extant maternal offshoot, namely haplogroup L0d, is represented by click-speaking forager peoples of southern Broadly defined as Khoesan, Khoesan are today largely restricted to the semidesert regions Namibia and Botswana, whereas archeological, historical, genetic evidence promotes a once broader southerly dispersal including southward migrating pastoralists indigenous marine-foragers. No data have been...
Genomic rearrangements are common in cancer, with demonstrated links to disease progression and treatment response. These can be complex, resulting fusions of multiple chromosomal fragments generation derivative chromosomes. Although methods exist for detecting individual fusions, they generally unable reconstruct complex chained events. To overcome these limitations, we adopted a new optical mapping approach, allowing megabase-length genome maps reconstructed rearranged genomes visualized...
Abstract Background African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from benefits of whole genome interrogation studies. Additionally, while structural variation (SV) highly prevalent, PCa genomic studies still biased towards small variant interrogation. Methods Using sequencing and best practice workflows, we performed comprehensive...
African ancestry is a significant risk factor for prostate cancer and advanced disease. Yet, genetic studies have largely been conducted outside the context of Sub-Saharan Africa, identifying 278 common variants contributing to multiethnic polygenic score, with rare focused on panel roughly 20 pathogenic genes. Based this knowledge, we are unable determine or differentiate status interrogating whole genome data 113 Black South men. To further assess potentially functional variant...