Circulating Methylated SEPT9 DNA in Plasma Is a Biomarker for Colorectal Cancer

被引：431

作者：

deVos, Theo ^{[1
]}

Tetzner, Reimo ^{[2
]}

Model, Fabian ^{[1
]}

Weiss, Gunter ^{[2
]}

Schuster, Matthias ^{[2
]}

Distler, Juergen ^{[2
]}

Steiger, Kathryn V. ^{[1
]}

Gruetzmann, Robert ^{[3
]}

Pilarsky, Christian ^{[3
]}

Habermann, Jens K. ^{[4
]}

Fleshner, Phillip R. ^{[5
]}

Oubre, Benton M. ^{[6
]}

Day, Robert ^{[1
]}

Sledziewski, Andrew Z. ^{[1
]}

Lofton-Day, Catherine ^{[1
]}

机构：

[1] Epigenomics Inc, Seattle, WA 98101 USA

[2] Epigen AG, Berlin, Germany

[3] Univ Hosp Carl Gustav Carus Dresden, Dept Visceral Thorac & Vasc Surg, Dresden, Germany

[4] Univ Hosp Schleswig Holstein, Dept Surg, Lubeck, Germany

[5] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[6] Gastroenterol Associates LLC, Baton Rouge, LA USA

来源：

CLINICAL CHEMISTRY | 2009年 / 55卷 / 07期

关键词：

TUMOR-SUPPRESSOR GENES; BLOOD; QUANTIFICATION; SERUM; MUTATIONS; NEOPLASIA; CARCINOMA; STOOL; TESTS; ASSAY;

D O I：

10.1373/clinchem.2008.115808

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

BACKGROUND: The presence of aberrantly methylated SEPT9 DNA in plasma is highly correlated with the occurrence of colorectal cancer. We report the development of a new SEPT9 biomarker assay and its validation in case-control studies. The development of such a minimally invasive blood-based test may help to reduce the current gap in screening coverage. METHODS: A new SEPT9 DNA methylation assay was developed for plasma. The assay comprised plasma DNA extraction, bisulfite conversion of DNA, purification of-bisulfite-converted DNA, quantification of converted DNA by real-time PCR, and measurement of SEPT9 methylation by real-time PCR. Performance of the SEPT9 assay was established in a study of 97 cases with verified colorectal cancer and 172 healthy controls as verified by colonoscopy. Performance based on predetermined algorithms was validated in an independent blinded study with 90 cases and 155 controls. RESULTS: The SEPT9 assay workflow yielded 1.9 mu g/L (CI 1.3-3.0) circulating plasma DNA following bisulfite conversion, a recovery of 45%-50% of genomic DNA, similar to yields in previous studies. The SEPT9 assay successfully identified 72% of cancers at a specificity of 93% in the training study and 68% of cancers at a specificity of 89% in the testing study. CONCLUSIONS: Circulating methylated SEPT9 DNA, as measured in the new (m)SEPT9 assay, is a valuable biomarker for minimally invasive detection of colorectal cancer. The new assay is amenable to automation an standardized use in the clinical laboratory. (C) 2009 American Association for Clinical Chemistry

引用

页码：1337 / 1346

页数：10

共 28 条

[1] Stool DNA and occult blood testing for screen detection of colorectal neoplasia [J].

Ahlquist, David A. ;

Sargent, Daniel J. ;

Loprinzi, Charles L. ;

Levin, Theodore R. ;

Rex, Douglas K. ;

Ahnen, Dennis J. ;

Knigge, Kandice ;

Lance, Peter ;

Burgart, Lawrence J. ;

Hamilton, Stanley R. ;

Allison, James E. ;

Lawson, Michael J. ;

Devens, Mary E. ;

Harrington, Jonathan J. ;

Hillman, Shauna L. .

ANNALS OF INTERNAL MEDICINE, 2008, 149 (07) :441-W81

[2] Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics [J].

Allison, James E. ;

Sakoda, Lori C. ;

Levin, Theodore R. ;

Tucker, Jo P. ;

Tekawa, Irene S. ;

Cuff, Thomas ;

Pauly, Mary Pat ;

Shlager, Lyle ;

Palitz, Albert M. ;

Zhao, Wei K. ;

Schwartz, J. Sanford ;

Ransohoff, David F. ;

Selby, Joseph V. .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2007, 99 (19) :1462-1470

[3]

[Anonymous], 2001, Rapid Cycle Real-Time PCR [Internet], DOI [DOI 10.1007/978-3-642-59524-0_3, 10.1007/978-3-642-59524-0_3]

[4] Frequently methylated tumor suppressor genes in head and neck squamous cell carcinoma [J].

Bennett, Kristi L. ;

Karpenko, Matthew ;

Lin, Mau-ting ;

Claus, Rainer ;

Arab, Khelifa ;

Dyckhoff, Gerhard ;

Plinkert, Peter ;

Herpel, Esther ;

Smiraglia, Dominic ;

Plass, Christoph .

CANCER RESEARCH, 2008, 68 (12) :4494-4499

[5] Free circulating DNA as possible tumour marker in colorectal cancer [J].

Boni, L. ;

Cassinotti, E. ;

Canziani, M. ;

Dionigi, G. ;

Rovera, F. ;

Dionigi, R. .

SURGICAL ONCOLOGY-OXFORD, 2007, 16 :S29-S31

[6] Altered expression of the septin gene, SEPT9, in ovarian neoplasia [J].

Burrows, JF ;

Chanduloy, S ;

McIlhatton, MA ;

Nagar, H ;

Yeates, K ;

Donaghy, P ;

Price, J ;

Godwin, AK ;

Johnston, PG ;

Russell, SHE .

JOURNAL OF PATHOLOGY, 2003, 201 (04) :581-588

[7] Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma [J].

Chan, K. C. Allen ;

Lai, Paul B. S. ;

Mok, Tony S. K. ;

Chan, Henry L. Y. ;

Ding, Chunming ;

Yeung, S. W. ;

Lo, Y. M. Dennis .

CLINICAL CHEMISTRY, 2008, 54 (09) :1528-1536

[8] Convergence of mutation and epigenetic alterations identifies common genes in cancer that predict for poor prognosis [J].

Chan, Timothy A. ;

Glockner, Sabine ;

Yi, Joo Mi ;

Chen, Wei ;

Van Neste, Leander ;

Cope, Leslie ;

Herman, James G. ;

Velculescu, Victor ;

Schuebel, Kornel E. ;

Ahuja, Nita ;

Baylin, Stephen B. .

PLOS MEDICINE, 2008, 5 (05) :823-838

[9]

Chiu RWK, 2001, CLIN CHEM, V47, P1607

[10] A real-time PCR assay for DNA-methylation using methylation-specific blockers [J].

Cottrell, SE ;

Distler, J ;

Goodman, NS ;

Mooney, SH ;

Kluth, A ;

Olek, A ;

Schwope, I ;

Tetzner, R ;

Ziebarth, H ;

Berlin, K .

NUCLEIC ACIDS RESEARCH, 2004, 32 (01) :e10

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