Methylation of the candidate biomarker TCF21 is very frequent across a spectrum of early-stage nonsmall cell lung cancers

Authors

  • Kristy L. Richards PhD, MD,

    1. Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina
    3. Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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  • Baili Zhang MS,

    1. Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Menghong Sun PhD,

    1. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Wenli Dong PhD,

    1. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Jennifer Churchill BS,

    1. Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Linda L. Bachinski PhD,

    1. Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Charmaine D. Wilson MS,

    1. Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Keith A. Baggerly PhD,

    1. Department of Bioinformatics and Computational Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Guosheng Yin PhD,

    1. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • D. Neil Hayes MD, MPH,

    1. Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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  • Ignacio I. Wistuba MD,

    1. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Ralf Krahe PhD

    Corresponding author
    1. Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Genetics, Unit 1010, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030
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    • Fax: (713) 834-6319


Abstract

BACKGROUND:

The transcription factor TCF21 is involved in mesenchymal-to-epithelial differentiation and was shown to be aberrantly hypermethylated in lung and head and neck cancers. Because of its reported high frequency of hypermethylation in lung cancer, further characterization of the stages and types of nonsmall cell lung cancer (NSCLC) that are hypermethylated and the frequency of hypermethylation and associated “second hits” were assessed.

METHODS:

TCF21 promoter hypermethylation in 105 NSCLC including various stages and histologies in smokers and nonsmokers was determined. In addition, TCF21 loss of heterozygosity and mutational status were examined. Twenty-two cancer cell lines from varied tissue origins were also assayed. The NSCLC results were validated and expanded by examining TCF21 immunohistochemical expression on a tissue microarray containing 300 NSCLC cases.

RESULTS:

Overall, 81% of NSCLC samples showed TCF21 promoter hypermethylation, and 84% showed decreased TCF21 protein expression. Multivariate analysis showed that TCF21 expression, although below normal in both histologies, was lower in adenocarcinoma than in squamous cell carcinoma and was not independently correlated with sex, smoking, and EGFR mutation status or with clinical outcome. Cell lines from other cancer types also showed frequent TCF21 promoter hypermethylation.

CONCLUSIONS:

Hypermethylation and decreased expression of TCF21 were tumor specific and very frequent in all NSCLCs, even early-stage disease, thus making TCF21 a potential candidate methylation biomarker for early-stage NSCLC screening. TCF21 hypermethylation in a variety of tumor cell lines suggests it may also be a valuable methylation biomarker in other tumor types. Cancer 2011. © 2010 American Cancer Society.

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