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DNA methylation biomarker candidates for early detection of colon cancer

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Tumor Biology

Abstract

Promoter CpG island hypermethylation of tumor suppressor genes is a common hallmark of all human cancers. Many researchers have been looking for potential epigenetic therapeutic targets in cancer using gene expression profiling with DNA microarray approaches. Our recent genome-wide platform of CpG island hypermethylation and gene expression in colorectal cancer (CRC) cell lines revealed that FBN2 and TCERG1L gene silencing is associated with DNA hypermethylation of a CpG island in the promoter region. In this study, promoter DNA hypermethylation of FBN2 and TCERG1L in CRC occurs as an early and cancer-specific event in colorectal cancer. Both genes showed high frequency of methylation in colon cancer cell lines (>80% for both of genes), adenomas (77% for FBN2, 90% for TCERG1L, n = 39), and carcinomas (86% for FBN2, 99% for TCERG1L, n = 124). Bisulfite sequencing confirmed cancer-specific methylation of FBN2 and TCERG1L of promoters in colon cancer cell line and cancers but not in normal colon. Methylation of FBN2 and TCERG1L is accompanied by downregulation in cell lines and in primary tumors as described in the Oncomine™ website. Together, our results suggest that gene silencing of FBN2 and TCERG1L is associated with promoter DNA hypermethylation in CRC tumors and may be excellent biomarkers for the early detection of CRC.

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Acknowledgments

The study is supported by the National R&D program (50595 and 50596) through the Dongnam Institute of Radiological & Medical Sciences (DIRAMS) funded by the Korean Ministry of Education, Science and Technology. This study is also supported by NIH/NCI K23CA127141, American College of Surgeons/Society of University Surgeons Career Development Award and the Jeannik M. Littlefield-AACR grant in metastatic colon cancer research. We thank the Johns Hopkins Cancer Registry for the assistance with the primary cancer databases.

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Authors and Affiliations

  1. Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, South Korea

    Joo Mi Yi, Kyu Heo & Kwang Mo Yang

  2. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA

    Mashaal Dhir, Angela A. Guzzetta & Nita Ahuja

  3. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA

    Christine A. Iacobuzio-Donahue

  4. Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan

    Hiromu Suzuki & Minoru Toyota

  5. Department of Pharmacy, College of Pharmacy, Gacheon University of Medicine and Science, Incheon, South Korea

    Hwan-Mook Kim

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  1. Joo Mi Yi
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  2. Mashaal Dhir
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Correspondence to Joo Mi Yi, Hwan-Mook Kim or Nita Ahuja.

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Authors Joo Mi Yi, Hwan Mook Kim, and Nita Ahuja contributed equally for this manuscript.

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Yi, J.M., Dhir, M., Guzzetta, A.A. et al. DNA methylation biomarker candidates for early detection of colon cancer. Tumor Biol. 33, 363–372 (2012). https://doi.org/10.1007/s13277-011-0302-2

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  • DOI: https://doi.org/10.1007/s13277-011-0302-2

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