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Article
Open AccessPrediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer
No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests bu...
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Article
Phase 1b study of enzalutamide plus CC-115, a dual mTORC1/2 and DNA-PK inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC)
CC-115, a dual mTORC1/2 and DNA-PK inhibitor, has promising antitumour activity when combined with androgen receptor (AR) inhibition in pre-clinical models.
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Article
Multiregion sampling of de novo metastatic prostate cancer reveals complex polyclonality and augments clinical genoty**
De novo metastatic prostate cancer is highly aggressive, but the paucity of routinely collected tissue has hindered genomic stratification and precision oncology. Here, we leveraged a rare study of surgical in...
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Article
Open AccessA generalizable machine learning framework for classifying DNA repair defects using ctDNA exomes
Specific classes of DNA damage repair (DDR) defect can drive sensitivity to emerging therapies for metastatic prostate cancer. However, biomarker approaches based on DDR gene sequencing do not accurately predi...
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Article
Open AccessThe cell-free DNA methylome captures distinctions between localized and metastatic prostate tumors
Metastatic prostate cancer remains a major clinical challenge and metastatic lesions are highly heterogeneous and difficult to biopsy. Liquid biopsy provides opportunities to gain insights into the underlying ...
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Article
Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer
Circulating tumour DNA (ctDNA) in blood plasma is an emerging tool for clinical cancer genoty** and longitudinal disease monitoring1. However, owing to past emphasis on targeted and low-resolution profiling app...
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Article
Clinical implications of genomic alterations in metastatic prostate cancer
There has been a rapid expansion in treatment options for the management of metastatic prostate cancer, but individual patient outcomes can be variable due to inter-patient tumor heterogeneity. Fortunately, th...
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Article
Building confidence in circulating tumour DNA assays for metastatic castration-resistant prostate cancer
Genomic alterations in metastatic castration-resistant prostate cancer can be identified in plasma circulating tumour DNA. A large cohort analysis shows reliable detection of clinically relevant alterations th...
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Article
Open AccessCell-free DNA concentration and fragment size as a biomarker for prostate cancer
Prostate cancer is the most commonly diagnosed neoplasm in American men. Although existing biomarkers may detect localized prostate cancer, additional strategies are necessary for improving detection and ident...
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Article
Open AccessPlasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer
Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment op...
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Article
The DNA methylation landscape of advanced prostate cancer
Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep w...
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Article
Open AccessEvaluating the quantity, quality and size distribution of cell-free DNA by multiplex droplet digital PCR
Cell-free DNA (cfDNA) has become a comprehensive biomarker in the fields of non-invasive cancer detection and monitoring, organ transplantation, prenatal genetic testing and pathogen detection. While cfDNA sam...
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Article
Open AccessConcurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer
Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1 tumor predisposition syndrome (TPDS). BAP1 TPDS is associated with an increased risk of uveal and cutaneous melanoma, meso...
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Article
Open AccessFrequent mutation of the FOXA1 untranslated region in prostate cancer
Prostate cancer has a low somatic mutation rate but non-coding regions remain underexplored. We sequenced the untranslated regions (UTRs) of 72 established driver genes in 428 patients with metastatic prostate...
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Article
Unravelling disparate roles of NOTCH in bladder cancer
The Notch pathway has been implicated in both oncogenic and tumour-suppressive roles in cancer depending on the tissue type and cellular context. However, until recently, little was known about the pathway in ...
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Article
Open AccessHer2 alterations in muscle-invasive bladder cancer: Patient selection beyond protein expression for targeted therapy
Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing...
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Article
Open AccessDiscovery of a Metastatic Immune Escape Mechanism Initiated by the Loss of Expression of the Tumour Biomarker Interleukin-33
A new paradigm for understanding immune-surveillance and immune escape in cancer is described here. Metastatic carcinomas express reduced levels of IL-33 and diminished levels of antigen processing machinery (...
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Article
Open AccessFunctional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients
The androgen receptor (AR) is a pivotal drug target for the treatment of prostate cancer, including its lethal castration-resistant (CRPC) form. All current non-steroidal AR antagonists, such as hydroxyflutami...
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Chapter and Conference Paper
Clonality Inference from Single Tumor Samples Using Low Coverage Sequence Data
Inference of intra-tumor heterogeneity can provide valuable insight into cancer evolution. Somatic mutations detected by sequencing can help estimate the purity of a tumor sample and reconstruct its subclonal ...
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Article
Open AccessHeterogeneity in the inter-tumor transcriptome of high risk prostate cancer
Genomic analyses of hundreds of prostate tumors have defined a diverse landscape of mutations and genome rearrangements, but the transcriptomic effect of this complexity is less well understood, particularly a...
