Methylation of TFPI2 in stool DNA: A potential novel biomarker for the detection of colorectal cancer

Sabine C. Glöckner; Mashaal Dhir; Mi Yi Joo; Kelly E. McGarvey; Leander Van Neste; Joost Louwagie; Timothy A. Chan; Wolfram Kleeberger; Adriaan P. De Bruïne; Kim M. Smits; Carolina A.J. Khalid-de Bakker; Daisy M.A.E. Jonkers; Reinhold W. Stockbrügger; Gerrit A. Meijer; Frank A. Oort; Christine Iacobuzio-Donahue; Katja Bierau; James G. Herman; Stephen B. Baylin; Manon Van Engeland; Kornel E. Schuebel; Nita Ahuja

doi:10.1158/0008-5472.CAN-08-0142

Methylation of TFPI2 in stool DNA: A potential novel biomarker for the detection of colorectal cancer

Sabine C. Glöckner, Mashaal Dhir, Mi Yi Joo, Kelly E. McGarvey, Leander Van Neste, Joost Louwagie, Timothy A. Chan, Wolfram Kleeberger, Adriaan P. De Bruïne, Kim M. Smits, Carolina A.J. Khalid-de Bakker, Daisy M.A.E. Jonkers, Reinhold W. Stockbrügger, Gerrit A. Meijer, Frank A. Oort, Christine Iacobuzio-Donahue, Katja Bierau, James G. Herman, Stephen B. Baylin, Manon Van EngelandKornel E. Schuebel, Nita Ahuja

School of Medicine

Research output: Contribution to journal › Article › peer-review

176 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	4691-4699
Number of pages	9
Journal	Cancer Research
Volume	69
Issue number	11
DOIs	https://doi.org/10.1158/0008-5472.CAN-08-0142
State	Published - Jun 1 2009

ASJC Scopus subject areas

Oncology
Cancer Research

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Glöckner, S. C., Dhir, M., Joo, M. Y., McGarvey, K. E., Van Neste, L., Louwagie, J., Chan, T. A., Kleeberger, W., De Bruïne, A. P., Smits, K. M., Khalid-de Bakker, C. A. J., Jonkers, D. M. A. E., Stockbrügger, R. W., Meijer, G. A., Oort, F. A., Iacobuzio-Donahue, C., Bierau, K., Herman, J. G., Baylin, S. B., ... Ahuja, N. (2009). Methylation of TFPI2 in stool DNA: A potential novel biomarker for the detection of colorectal cancer. Cancer Research, 69(11), 4691-4699. https://doi.org/10.1158/0008-5472.CAN-08-0142

Glöckner, SC, Dhir, M, Joo, MY, McGarvey, KE, Van Neste, L, Louwagie, J, Chan, TA, Kleeberger, W, De Bruïne, AP, Smits, KM, Khalid-de Bakker, CAJ, Jonkers, DMAE, Stockbrügger, RW, Meijer, GA, Oort, FA, Iacobuzio-Donahue, C, Bierau, K, Herman, JG, Baylin, SB, Van Engeland, M, Schuebel, KE & Ahuja, N 2009, 'Methylation of TFPI2 in stool DNA: A potential novel biomarker for the detection of colorectal cancer', Cancer Research, vol. 69, no. 11, pp. 4691-4699. https://doi.org/10.1158/0008-5472.CAN-08-0142

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abstract = "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.",

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T2 - A potential novel biomarker for the detection of colorectal cancer

AU - Glöckner, Sabine C.

AU - Dhir, Mashaal

AU - Joo, Mi Yi

AU - McGarvey, Kelly E.

AU - Van Neste, Leander

AU - Louwagie, Joost

AU - Chan, Timothy A.

AU - Kleeberger, Wolfram

AU - De Bruïne, Adriaan P.

AU - Smits, Kim M.

AU - Khalid-de Bakker, Carolina A.J.

AU - Jonkers, Daisy M.A.E.

AU - Stockbrügger, Reinhold W.

AU - Meijer, Gerrit A.

AU - Oort, Frank A.

AU - Iacobuzio-Donahue, Christine

AU - Bierau, Katja

AU - Herman, James G.

AU - Baylin, Stephen B.

AU - Van Engeland, Manon

AU - Schuebel, Kornel E.

AU - Ahuja, Nita

PY - 2009/6/1

Y1 - 2009/6/1

N2 - 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.

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Methylation of TFPI2 in stool DNA: A potential novel biomarker for the detection of colorectal cancer

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