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      Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing.

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          Abstract

          Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively.

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          Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer.

          Johann de Bono, Howard Scher, R. Montgomery … (2008)
          A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining the prognostic utility of CTC measurement before initiating therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes and OS at these and other time points. Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetermined Favorable or Unfavorable groups ( or =5 CTC/7.5mL). Two hundred thirty-one of 276 enrolled patients (84%) were evaluable. Patients with Unfavorable pretreatment CTC (57%) had shorter OS (median OS, 11.5 versus 21.7 months; Cox hazard ratio, 3.3; P 26 to 9.3 months). CTC are the most accurate and independent predictor of OS in CRPC. These data led to Food and Drug Administration clearance of this assay for the evaluation of CRPC.
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            Performance comparison of benchtop high-throughput sequencing platforms.

            Nicholas Loman, Raju V. Misra, Timothy Dallman … (2012)
            Three benchtop high-throughput sequencing instruments are now available. The 454 GS Junior (Roche), MiSeq (Illumina) and Ion Torrent PGM (Life Technologies) are laser-printer sized and offer modest set-up and running costs. Each instrument can generate data required for a draft bacterial genome sequence in days, making them attractive for identifying and characterizing pathogens in the clinical setting. We compared the performance of these instruments by sequencing an isolate of Escherichia coli O104:H4, which caused an outbreak of food poisoning in Germany in 2011. The MiSeq had the highest throughput per run (1.6 Gb/run, 60 Mb/h) and lowest error rates. The 454 GS Junior generated the longest reads (up to 600 bases) and most contiguous assemblies but had the lowest throughput (70 Mb/run, 9 Mb/h). Run in 100-bp mode, the Ion Torrent PGM had the highest throughput (80–100 Mb/h). Unlike the MiSeq, the Ion Torrent PGM and 454 GS Junior both produced homopolymer-associated indel errors (1.5 and 0.38 errors per 100 bases, respectively).
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              Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood.

              H Christina Fan, Yair Blumenfeld, Usha Chitkara … (2008)
              We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Genome Med
                Title: Genome medicine
                Publisher: Springer Science and Business Media LLC
                ISSN: 1756-994X
                ISSN (Print): 1756-994X
                Publication date (Electronic): 2013
                Volume: 5
                Issue: 4
                Affiliations
                [1 ] Institute of Human Genetics, Medical University of Graz, Harrachgasse 21/8, A-8010 Graz, Austria.
                [2 ] Department of Urology, Medical University of Graz, Auenbruggerplatz 5/6, A-8036 Graz, Austria.
                [3 ] Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 2, A-8036 Graz, Austria.
                [4 ] Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, A-8036 Graz, Austria.
                [5 ] Division of Oncology, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.
                [6 ] Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria.
                [7 ] Institute of Tumor Biology, University Medical Center Hamburg Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
                Article
                Publisher Item ID: gm434
                DOI: 10.1186/gm434
                PMC ID: 3707016
                PubMed ID: 23561577
                SO-VID: 8346e814-a2b1-4802-a5af-7791dc1299ee
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