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Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay

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Item Type:Article
Title:Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay
Creators Name:Gruetzmann, R. and Molnar, B. and Pilarsky, C. and Habermann, J.K. and Schlag, P.M. and Saeger, H.D. and Miehlke, S. and Stolz, T. and Model, F. and Roblick, U.J. and Bruch, H.P. and Koch, R. and Liebenberg, V. and Devos, T. and Song, X. and Day, R.H. and Sledziewski, A.Z. and Lofton-Day, C.
Abstract:BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. METHODOLOGY/PRINCIPAL FINDINGS: Using a PCR assay for analysis of Septin 9 (SEPT9) hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls) and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls). 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48%) and 7/102 controls (7%). In the test study 73/126 CRCs (58%) and 18/183 control samples (10%) were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected) while maintaining 90% specificity (19/183 for controls). Positive rates for plasmas from the other cancers (11/96) and non-cancerous conditions (41/315) were low. The rate of polyp detection (>1 cm) was approximately 20%. CONCLUSIONS/SIGNIFICANCE: Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted.
Keywords:Algorithms, Case-Control Studies, Colorectal Neoplasms, DNA Methylation, GTP Phosphohydrolases, Mass Screening, Polymerase Chain Reaction, Sensitivity and Specificity, Treatment Outcome
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:3
Number:11
Page Range:e3759
Date:19 November 2008
Official Publication:https://doi.org/10.1371/journal.pone.0003759
PubMed:View item in PubMed

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