Tumor Biology

, Volume 33, Issue 2, pp 363–372

DNA methylation biomarker candidates for early detection of colon cancer

  • Joo Mi Yi
  • Mashaal Dhir
  • Angela A. Guzzetta
  • Christine A. Iacobuzio-Donahue
  • Kyu Heo
  • Kwang Mo Yang
  • Hiromu Suzuki
  • Minoru Toyota
  • Hwan-Mook Kim
  • Nita Ahuja
Research Article

DOI: 10.1007/s13277-011-0302-2

Cite this article as:
Yi, J.M., Dhir, M., Guzzetta, A.A. et al. Tumor Biol. (2012) 33: 363. doi:10.1007/s13277-011-0302-2

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.

Keywords

DNA hypermethylationBiomarkerEarly detectionColorectal Cancer (CRC)FBN2TCERGIL

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Joo Mi Yi
    • 1
  • Mashaal Dhir
    • 2
  • Angela A. Guzzetta
    • 2
  • Christine A. Iacobuzio-Donahue
    • 3
  • Kyu Heo
    • 1
  • Kwang Mo Yang
    • 1
  • Hiromu Suzuki
    • 4
  • Minoru Toyota
    • 4
  • Hwan-Mook Kim
    • 5
  • Nita Ahuja
    • 2
  1. 1.Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS)BusanSouth Korea
  2. 2.Department of SurgeryThe Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of PathologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Department of Molecular BiologySapporo Medical UniversitySapporoJapan
  5. 5.Department of Pharmacy, College of PharmacyGacheon University of Medicine and ScienceIncheonSouth Korea