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Methylation of TFPI2 in Stool DNA: A Potential Novel Biomarker for the Detection of Colorectal Cancer

Departments of ¹ Surgery, ² Oncology, and ³ Pathology, Johns Hopkins University, Baltimore, Maryland; ⁴ Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; ⁵ Oncomethylome Sciences SA, Liege, Belgium; ⁶ Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York; ⁷ Department of Pathology, University of Regensburg, Regensburg, Germany; ⁸ Department of Pathology, GROW-School for Oncology and Developmental Biology, and ⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands; and Departments of ¹⁰ Pathology and ¹¹ Gastroenterology, VU University Medical Center, Amsterdam, the Netherlands

Requests for reprints: Nita Ahuja, Johns Hopkins Medical Institutes, CRB1 Room 342, 1650 Orleans Street, Baltimore, MD 21287. Phone: 410-502-6135; Fax: 410-502-0987; E-mail: nahuja1{at}jhmi.edu or Kornel E. Schuebel, E-mail: kornels{at}mail.nih.gov or Manon Van Engeland, E-mail: M.vanEngeland{at}PATH.unimaas.nl.

Key Words: TFPI2 • methylation • colorectal cancer • stool DNA

We have used a gene expression array–based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)–marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA–based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future. [Cancer Res 2009;69(11):4691–9]

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