Tumor Biology

, Volume 33, Issue 2, pp 287–296

DNA methylation biomarkers for lung cancer

  • Tibor A. Rauch
  • Zunde Wang
  • Xiwei Wu
  • Kemp H. Kernstine
  • Arthur D. Riggs
  • Gerd P. Pfeifer
Research Article

DOI: 10.1007/s13277-011-0282-2

Cite this article as:
Rauch, T.A., Wang, Z., Wu, X. et al. Tumor Biol. (2012) 33: 287. doi:10.1007/s13277-011-0282-2

Abstract

Changes in DNA methylation patterns are an important characteristic of human cancer including lung cancer. In particular, hypermethylation of CpG islands is a signature of malignant progression. Methylated CpG islands are promising diagnostic markers for the early detection of cancer. However, the full extent and sequence context of DNA hypermethylation in lung cancer has remained unknown. We have used the methylated CpG island recovery assay and high-resolution microarray analysis to find hypermethylated CpG islands in squamous cell carcinomas (SCC) and adenocarcinomas of the lung. Each tumor contained several hundred hypermethylated CpG islands. In an initial microarray screen, 36 CpG islands were methylated in five of five (=100%) of the SCC tumors tested and 52 CpG islands were methylated in at least 75% of the adenocarcinomas tested (n = 8). Using sodium-bisulfite-based approaches, 12 CpG islands (associated with the BARHL2, EVX2, IRX2, MEIS1, MSX1, NR2E1, OC2, OSR1, OTX1, PAX6, TFAP2A, and ZNF577 genes) were confirmed to be methylated in 85% to 100% of the squamous cell carcinomas and 11 CpG islands (associated with the CHAD, DLX4, GRIK2, KCNG3, NR2E1, OSR1, OTX1, OTX2, PROX1, RUNX1, and VAX1 genes) were methylated in >80% of the adenocarcinomas. From the list of genes that were methylated in lung adenocarcinomas, we identified the gene FAT4 and found that this gene was methylated in 39% of the tumors. FAT4 is the closest mammalian homologue of the Drosophila tumor suppressor Fat which is an important component of the Hippo growth control pathway. Many of these newly discovered methylated CpG islands hold promise for becoming biomarkers for the early detection of lung cancer.

Keywords

DNA methylation CpG islands Methylation marker Lung cancer FAT4 

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  • Tibor A. Rauch
    • 1
    • 4
  • Zunde Wang
    • 1
  • Xiwei Wu
    • 2
  • Kemp H. Kernstine
    • 3
  • Arthur D. Riggs
    • 1
  • Gerd P. Pfeifer
    • 1
  1. 1.Division of BiologyBeckman Research Institute of the City of HopeDuarteUSA
  2. 2.Department of Information SciencesBeckman Research Institute of the City of HopeDuarteUSA
  3. 3.Division of Thoracic SurgeryUniversity of Texas, Southwestern Medical CenterDallasUSA
  4. 4.Section of Molecular Medicine, Department of Orthopedic SurgeryRush University Medical CenterChicagoUSA

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