Plasma tumour DNA as an early indicator of treatment response in metastatic castration-resistant prostate cancer.

Background: Plasma tumour DNA (ptDNA) levels on treatment are associated with response in a variety of cancers. However, the role of ptDNA in prostate cancer monitoring remains largely unexplored. Here we characterised on-treatment ptDNA dynamics and evaluated its potential for early assessment of therapy efficacy for metastatic castration-resistant prostate cancer (mCRPC).

Circulating cell-free DNA: Translating prostate cancer genomics into clinical care.

Only in the past decade tremendous advances have been made in understanding prostate cancer genomics and consequently in applying new treatment strategies. As options regarding treatments are increasing so are the challenges in selecting the right treatment option for each patient and not the least, understanding the optimal time-point and sequence of applying available treatments. Critically, without reliable methods that enable sequential monitoring of evolving genotypes in individual patients, we will never reach effective personalised driven treatment approaches.

Identification of single nucleotide variants using position-specific error estimation in deep sequencing data.

Background: Targeted deep sequencing is a highly effective technology to identify known and novel single nucleotide variants (SNVs) with many applications in translational medicine, disease monitoring and cancer profiling. However, identification of SNVs using deep sequencing data is a challenging computational problem as different sequencing artifacts limit the analytical sensitivity of SNV detection, especially at low variant allele frequencies (VAFs).

Methods: To address the problem of relatively high noise levels in amplicon-based deep sequencing data (e.

Plasma AR and abiraterone-resistant prostate cancer.

Androgen receptor (AR) gene aberrations are rare in prostate cancer before primary hormone treatment but emerge with castration resistance. To determine AR gene status using a minimally invasive assay that could have broad clinical utility, we developed a targeted next-generation sequencing approach amenable to plasma DNA, covering all AR coding bases and genomic regions that are highly informative in prostate cancer. We sequenced 274 plasma samples from 97 castration-resistant prostate cancer patients treated with abiraterone at two institutions.

Serial Next-Generation Sequencing of Circulating Cell-Free DNA Evaluating Tumor Clone Response To Molecularly Targeted Drug Administration.

Purpose: We evaluated whether next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA) could be used for patient selection and as a tumor clone response biomarker in patients with advanced cancers participating in early-phase clinical trials of targeted drugs.

Experimental Design: Plasma samples from patients with known tumor mutations who completed at least two courses of investigational targeted therapy were collected monthly, until disease progression. NGS was performed sequentially on the Ion Torrent PGM platform.

ETS fusion genes in prostate cancer.

Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer.

A 36-gene signature predicts clinical progression in a subgroup of ERG-positive prostate cancers.

Background: The molecular basis of the clinical heterogeneity of prostate cancer (PCa) is not well understood.

Objective: The purpose of our study was to identify and characterize genes in a clinically relevant gene expression signature in a subgroup of primary PCa positive for transmembrane protease, serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG).

Design, Setting, And Participants: We studied gene expression profiles by unsupervised hierarchical clustering in 48 primary PCas from patients with a long clinical follow-up.