DNA methylation biomarkers for blood-based colorectal cancer screening

Catherine Lofton-Day, Fabian Model, Theo DeVos, Reimo Tetzner, Juergen Distler, Matthias Schuster, Xiaoling Song, Ralf Lesche, Volker Liebenberg, Matthias Ebert, B. Molnár, Robert Grützmann, Christian Pilarsky, Andrew Sledziewski

Research output: Contribution to journalArticle

309 Citations (Scopus)

Abstract

BACKGROUND: Sensitive, specific blood-based tests are difficult to develop unless steps are taken to maximize performance characteristics at every stage of marker discovery and development. We describe a sieving strategy for identifying high-performing marker assays that detect colorectal cancer (CRC)-specific methylated DNA in plasma. METHODS: We first used restriction enzyme-based discovery methods to identify marker candidates with obviously different methylation patterns in CRC tissue and nonpathologic tissue. We then used a selection process incorporating microarrays and/or real-time PCR analysis of tissue samples to further test marker candidates for maximum methylation in CRC tissue and minimum amplification in tissues from both healthy individuals and patients with other diseases. Real-time assays of 3 selected markers were validated with plasma samples from 133 CRC patients and 179 healthy control individuals in the same age range. RESULTS: Restriction enzyme-based testing identified 56 candidate markers. This group was reduced to 6 with microarray and real-time PCR testing. Three markers, TMEFF2, NGFR, and SEPT9, were tested with plasma samples. TMEFF2 methylation was detected in 65%[95% confidence interval, 56%-73%] of plasma samples from CRCpatients and not detected in 69% (62%-76%) of the controls. The corresponding results for NGFR were 51% (42%-60%) and 84% (77%-89%); for SEPT9, the values were 69% (60%-77%) and 86% (80%-91%). CONCLUSIONS: The stringent criteria applied at all steps of the selection and validation process enabled successful identification and ranking of blood-based marker candidates.

Original languageEnglish
Pages (from-to)414-423
Number of pages10
JournalClinical Chemistry
Volume54
Issue number2
DOIs
Publication statusPublished - 2008

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Biomarkers
DNA Methylation
Early Detection of Cancer
Colorectal Neoplasms
Screening
Blood
Methylation
Tissue
Plasmas
Microarrays
Real-Time Polymerase Chain Reaction
Assays
Hematologic Tests
Testing
Enzymes
Amplification
Confidence Intervals
DNA

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Lofton-Day, C., Model, F., DeVos, T., Tetzner, R., Distler, J., Schuster, M., ... Sledziewski, A. (2008). DNA methylation biomarkers for blood-based colorectal cancer screening. Clinical Chemistry, 54(2), 414-423. https://doi.org/10.1373/clinchem.2007.095992

DNA methylation biomarkers for blood-based colorectal cancer screening. / Lofton-Day, Catherine; Model, Fabian; DeVos, Theo; Tetzner, Reimo; Distler, Juergen; Schuster, Matthias; Song, Xiaoling; Lesche, Ralf; Liebenberg, Volker; Ebert, Matthias; Molnár, B.; Grützmann, Robert; Pilarsky, Christian; Sledziewski, Andrew.

In: Clinical Chemistry, Vol. 54, No. 2, 2008, p. 414-423.

Research output: Contribution to journalArticle

Lofton-Day, C, Model, F, DeVos, T, Tetzner, R, Distler, J, Schuster, M, Song, X, Lesche, R, Liebenberg, V, Ebert, M, Molnár, B, Grützmann, R, Pilarsky, C & Sledziewski, A 2008, 'DNA methylation biomarkers for blood-based colorectal cancer screening', Clinical Chemistry, vol. 54, no. 2, pp. 414-423. https://doi.org/10.1373/clinchem.2007.095992
Lofton-Day C, Model F, DeVos T, Tetzner R, Distler J, Schuster M et al. DNA methylation biomarkers for blood-based colorectal cancer screening. Clinical Chemistry. 2008;54(2):414-423. https://doi.org/10.1373/clinchem.2007.095992
Lofton-Day, Catherine ; Model, Fabian ; DeVos, Theo ; Tetzner, Reimo ; Distler, Juergen ; Schuster, Matthias ; Song, Xiaoling ; Lesche, Ralf ; Liebenberg, Volker ; Ebert, Matthias ; Molnár, B. ; Grützmann, Robert ; Pilarsky, Christian ; Sledziewski, Andrew. / DNA methylation biomarkers for blood-based colorectal cancer screening. In: Clinical Chemistry. 2008 ; Vol. 54, No. 2. pp. 414-423.
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