Abstract:
BACKGROUND:Genomic instability resulting in copy number variation is a hallmark of malignant transformation and may be identified through massive parallel sequencing. Tumor-specific cell free DNA (cfDNA) present in serum and plasma provides a real-time, easily accessible surrogate. METHODS:DNA was extracted from serum of 204 patients with prostate cancer (Gleason score 2-10), 207 male controls, and patients with benign hyperplasia (n = 10) and prostatitis (n = 10). DNA was amplified by use of random primers, tagged with molecular identifiers, sequenced on a SOLID system, and aligned to the human genome. We evaluated the number of sequence reads of cfDNA in sliding 100-kbp intervals for variation from controls. We used chromosomal regions with significant variations in alignment hits for their ability to segregate patients and matched controls. RESULTS:Using ROC curves to assess diagnostic performance, we evaluated the number of regions in a first subset (n = 177), with variations in alignment hits alone, provided an area under the curve (AUC) of 0.81 (95% CI 0.7-0.9, P < 0.001). Using 5 rounds of 10-fold cross-validation with the full data set, we established a final model that discriminated prostate cancer from controls with an AUC of 0.92 (0.87-0.95), reaching a diagnostic accuracy of 83%. Both benign prostatic hypertrophy and prostatitis could be distinguished from prostate cancer by use of cfDNA, with an accuracy of 90%. CONCLUSIONS:Assessment of a limited number of chromosomal structural instabilities by use of massive parallel sequencing of cfDNA was sufficient to distinguish between prostate cancer and controls. This large cohort demonstrates the utility of cfDNA in prostate cancer recently established in other malignant neoplasms.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Schütz E,Akbari MR,Beck J,Urnovitz H,Zhang WW,Bornemann-Kolatzki K,Mitchell WM,Nam RK,Narod SAdoi
10.1373/clinchem.2014.226571subject
Has Abstractpub_date
2015-01-01 00:00:00pages
239-48issue
1eissn
0009-9147issn
1530-8561pii
clinchem.2014.226571journal_volume
61pub_type
杂志文章abstract:BACKGROUND:Variability among assays used to measure intact parathyroid hormone (iPTH) is of particular concern because of the routine use of iPTH assay results to guide management of osteodystrophy and calcium metabolism in patients with end-stage renal disease (ESRD). The aim of this study was to determine the extent ...
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journal_title:Clinical chemistry
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journal_title:Clinical chemistry
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journal_title:Clinical chemistry
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doi:
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doi:
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journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
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doi:
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更新日期:2004-10-01 00:00:00
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doi:
更新日期:1987-10-01 00:00:00
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