Project description:Liquid biopsies offer significant potential for informing on cancer progression and therapeutic resistance via minimally invasive serial monitoring of genetic alterations. Although the cancer epigenome is a central driving force in most neoplasia, how well the tumour methylome can be monitored via liquid biopsies is relatively unknown. In this first of its kind study we made a direct comparison of two liquid biopsies: urine and blood, asking how well they represent the tumor methylome. Utilizing the Infinium Methylation EPIC BeadChip, we profiled DNA methylation in tissue, urine sediment and cell-free circulating DNA from four men with advanced stage prostate cancer. We show that both urine and plasma are viable surrogates for tumor tissue biopsies, capturing 78.63 and 62.21% of tumor-specific methylation alterations, respectively. We conclude that urine is an easily accessible and sensitive biofluid for the study of prostate cancer epigenomic alterations.
Project description:We used a groundbreaking epigenomic profiling technique developed in our laboratory, the 4f-SAMMY-seq, along with RNA-seq on 7 healthy biopsies and 18 prostate tumor biopsies. Our study represents the first direct examination of chromatin organization in patient-derived prostate biopsies. Leveraging differences in chromatin architecture, we identified a novel Prostate Cancer transcriptional signature associated with a favorable prognosis.
Project description:Standard clinicopathological variables are inadequate for optimal management of prostate cancer patients. While genomic classifiers have improved patient risk classification, the multifocality and heterogeneity of prostate cancer can confound pre-treatment assessment. The objective is to investigate the association of multiparametric (mp)MRI quantitative features with prostate cancer risk gene expression profiles in mpMRI-guided biopsies tissues.
Project description:Disease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive platform to study the dynamics of tumour progression. Our study aimed to investigate the dynamics of personal methylomic profiles of metastatic PCa (mPCa) patients, during disease progression and therapy administration. 52 plasma samples from 9 patients with mPCa were collected, longitudinally, over 13-21 months. After cell-free DNA (cfDNA) isolation, DNA methylation was profiled using the Infinium MethylationEPIC BeadChip and analysed using the minfi software. The top 5% most variable probes across time, within each individual, were utilised to study dynamic methylation patterns during disease progression and therapeutic response. Statistical testing was carried out to identify and validate ctDNA differentially methylated genes (DMGs). Personal cfDNA global methylation patterns were temporally stable throughout disease course. A proportion of analysed CpG sites presented a dynamic temporal pattern that was consistent with clinical events, such as therapy administration, and were prominently associated with immune response pathways. Study of ctDNA identified >2,000 DMGs with dynamic methylation patterns. We concluded that longitudinal assessment of cfDNA methylation in mPCa patients unveiled dynamic patterns associated with the occurrence of specific clinical events, thus highlighting the potential of using liquid biopsies to study PCa progression.