Publications by authors named "J J Alumkal"
Prostate cancer (PC) progresses from benign epithelium through pre-malignant lesions, localized tumors, metastatic dissemination, and castration-resistant stages, with some cases exhibiting phenotype plasticity under therapeutic pressure. However, high-resolution insights into how cell phenotypes evolve across successive stages of PC remain limited. Here, we present the Prostate Cancer Cell Atlas (PCCAT) by integrating ∼710,000 single cells from 197 human samples covering a spectrum of tumor stages.
View Article and Find Full Text PDFIntroduction: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration-resistant diagnosis. Optimal first-line therapy for those with different prognoses is unknown.
Methods: We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first-line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow-up through 2019.
Article Synopsis
- The study explores how three-dimensional genomic structure variations impact gene expression and mutation rates in metastatic castration-resistant prostate cancer, using a combination of advanced sequencing techniques on 80 biopsy samples.
- Findings revealed significant differences in gene expression, methylation patterns, and structural variations between different chromatin compartments, along with specific chromatin contact loss at the AR locus linked to poor treatment responses.
- The research identified distinct subtypes of tumors based on their methylation and gene expression profiles, suggesting that DNA interactions could contribute to structural variant formation, ultimately enhancing understanding of tumor behavior and treatment outcomes.
Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that resists therapy targeting androgen signaling, the primary driver of prostate cancer. mCRPC resists androgen receptor (AR) inhibitors by amplifying AR signaling or by evolving into therapy-resistant subtypes that do not depend on AR. Elucidation of the epigenetic underpinnings of these subtypes could provide important insights into the drivers of therapy resistance.
View Article and Find Full Text PDFTranscription factor (TF) proteins regulate gene activity by binding to regulatory regions, most importantly at gene promoters. Many genes have alternative promoters (APs) bound by distinct TFs. The role of differential TF activity at APs during tumour development is poorly understood.
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