Comprehensive Genomic Profiling of Cell-Free DNA in Men With Advanced Prostate Cancer: Differences in Genomic Landscape Based on Race

Reisinger, Raquel; Bilen, Mehmet Asım; Heath, Elisabeth I.; Nandagopal, Lakshminarayanan; Swami, Umang; Kessel, Adam; Jaeger, Ellen; Wesołowski, Sergiusz; Hernanadez, Edgar J; Chipman, Jonathan; Mack, Alleda; Ravindranathan, Deepak; Nussenzveig, Roberto; Yandell, Mark; Kohli, Manish; Lilly, Michael B.; Sartor, A. Oliver; Agarwal, Neeraj; Barata, Pedro C.

doi:10.1093/oncolo/oyac176

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…Another study revealed disparities in the adoption of cell-free fetal DNA (cffDNA) screening, particularly noting differences between Hispanic and White women [62]. Furthermore, investigations into the genomic landscape of cell-free DNA in men with advanced prostate cancer have unveiled distinctions based on race [63]. These findings collectively suggest noteworthy racial and ethnic variations in both cell-free DNA levels and the adoption of cf-DNA screening.…”

Section: Ethnic Differences In Cell-free Dnamentioning

confidence: 99%

Cell-Free DNA As Peripheral Biomarker of Alzheimer’s Disease

2024

Aging dis

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Alzheimer's disease (AD) and Alzheimer's disease-related disorders (ADRD) are progressive neurodegenerative diseases without cure. Alzheimer's disease occurs in 2 forms, early-onset familial AD and lateonset sporadic AD. Early-onset AD is a rare (~1%), autosomal dominant, caused by mutations in presenilin-1, presenilin-2, and amyloid precursor protein genes and the other is a late-onset, prevalent and is evolved due to ageassociated complex interactions between environmental and genetic factors, in addition to apolipoprotein E4 polymorphism. Cellular senescence, promoting the impairment of physical and mental functions is constituted to be the main cause of aging, the primary risk factor for AD, which results in progressive loss of cognitive function, memory, and visual-spatial skills for an individual to live or act independently. Despite significant progress in the understanding of the biology and pathophysiology of AD, we continue to lack definitive early detectable biomarkers and/or drug targets that can be used to delay the development of AD and ADRD in elderly populations. However, recent developments in the studies of DNA double-strand breaks result in the release of fragmented DNA into the bloodstream and contribute to higher levels of cell-free DNA (cf-DNA). This fragmented cf-DNA can be released into the bloodstream from various cell types, including normal cells and cells undergoing apoptosis or necrosis and elevated levels of cf-DNA in the blood have the potential to serve as blood blood-based biomarker for early detection of AD and ADRD. The overall goal of our study is to discuss the latest developments in circulating cell-free DNA into the blood in the progression of AD and ADRD. Our article summarized the status of research on double-strand breaks and circulating cell-free DNA in both healthy and disease states and how these recent developments can be used to develop early detectable biomarkers for AD and ADRD. Our article also discussed the impact of lifestyle and epigenetic factors that are involved in DNA double-strand breaks and circulating cell-free DNA in AD and ADRD.

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Section: Ethnic Differences In Cell-free Dnamentioning

confidence: 99%

Cell-Free DNA As Peripheral Biomarker of Alzheimer’s Disease

2024

Aging dis

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“…Furthermore, MYC amplification is associated with a higher Gleason grade and unfavorable prognosis in patients with PCa [148,149]. Interestingly, alterations in MYC are more frequently reported in black men than white men [149,150]. MYC overexpression was identified as an early event in PIN [151].…”

Section: Myc a Master Regulator Of Transcriptionmentioning

confidence: 99%

“…Beyond tissue analysis and imaging, MYC copy-number gain is detectable in cell-free DNA (cfDNA) isolated from blood [149,150] and urine [156], opening the potential of MYC to be used as a circulating biomarker. The detection of MYC levels in bodily fluids, such as blood or urine, may provide a less invasive method for diagnosing and monitoring PCa when compared to biopsy from a single site [156].…”

Section: Diagnostic Potential Of Mycmentioning

confidence: 99%

Transcription Factors in Prostate Cancer: Insights for Disease Development and Diagnostic and Therapeutic Approaches

Silva,

Tambwe,

Mahfouz

et al. 2024

Genes

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Transcription factors (TFs) are proteins essential for the regulation of gene expression, and they regulate the genes involved in different cellular processes, such as proliferation, differentiation, survival, and apoptosis. Although their expression is essential in normal physiological conditions, abnormal regulation of TFs plays critical role in several diseases, including cancer. In prostate cancer, the most common malignancy in men, TFs are known to play crucial roles in the initiation, progression, and resistance to therapy of the disease. Understanding the interplay between these TFs and their downstream targets provides insights into the molecular basis of prostate cancer pathogenesis. In this review, we discuss the involvement of key TFs, including the E26 Transformation-Specific (ETS) Family (ERG and SPDEF), NF-κB, Activating Protein-1 (AP-1), MYC, and androgen receptor (AR), in prostate cancer while focusing on the molecular mechanisms involved in prostate cancer development. We also discuss emerging diagnostic strategies, early detection, and risk stratification using TFs. Furthermore, we explore the development of therapeutic interventions targeting TF pathways, including the use of small molecule inhibitors, gene therapies, and immunotherapies, aimed at disrupting oncogenic TF signaling and improving patient outcomes. Understanding the complex regulation of TFs in prostate cancer provides valuable insights into disease biology, which ultimately may lead to advancing precision approaches for patients.

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“…Blood-based cfDNA analysis of the androgen receptor (AR) gene can help predict resistance to enzalutamide and abiraterone in metastatic castration-resistant prostate cancer (mCRPC) [28]. Furthermore, the genomic profiling of cfDNA has shed light on differences in the genomic landscape between Caucasian and African American PCa patients, highlighting a higher number of alterations in genes like AR, EGFR, MYC, FGFR1, and CTNNB1 in African American patients [29].…”

Section: Introductionmentioning

confidence: 99%

Detection of Cancer-Associated Gene Mutations in Urinary Cell-Free DNA among Prostate Cancer Patients in South Africa

Temilola,

Wium,

Paccez

et al. 2023

Genes

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Prostate cancer (PCa) is the most common cause of cancer death among African men. The presence of tumor-specific variations in cell-free DNA (cfDNA), such as mutations, microsatellite instability, and DNA methylation, has been explored as a source of biomarkers for cancer diagnosis. In this study, we investigated the diagnostic role of cfDNA among South African PCa patients. We performed whole exome sequencing (WES) of urinary cfDNA. We identified a novel panel of 31 significantly deregulated somatic mutated genes between PCa and benign prostatic hyperplasia (BPH). Additionally, we performed whole-genome sequencing (WGS) on matching PCa and normal prostate tissue in an independent PCa cohort from South Africa. Our results suggest that the mutations are of germline origin as they were also found in the normal prostate tissue. In conclusion, our study contributes to the knowledge of cfDNA as a biomarker for diagnosing PCa in the South African population.

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Comprehensive Genomic Profiling of Cell-Free DNA in Men With Advanced Prostate Cancer: Differences in Genomic Landscape Based on Race

Cited by 5 publications

References 9 publications

Cell-Free DNA As Peripheral Biomarker of Alzheimer’s Disease

Cell-Free DNA As Peripheral Biomarker of Alzheimer’s Disease

Transcription Factors in Prostate Cancer: Insights for Disease Development and Diagnostic and Therapeutic Approaches

Detection of Cancer-Associated Gene Mutations in Urinary Cell-Free DNA among Prostate Cancer Patients in South Africa

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