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CpG Methylation of Transcription Factor 4 in Gastric Carcinoma

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Epigenetic silencing of tumor-related genes by CpG island methylation is an important mechanism for the development of many tumors, including gastric carcinoma. Deregulation of transcription factor 4 (TCF4) by promoter methylation was recently shown to play a key role in gastric carcinogenesis.

Methods

The extent of methylation in the TCF4 promoter was assessed using methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PS) in 120 gastric carcinoma (GC) samples collected during gastrectomy, and in 40 normal gastric mucosa samples.

Results

The PS analysis of GCs revealed a higher frequency of TCF4 methylation (75.8%; 91/120). The methylation frequency for TCF4 by both MSP and PS techniques was significantly higher in advanced (75.0 and 91.7%, respectively) compared with early (60.0 and 60.0%, respectively, p < 0.05) GCs. There was a significant difference in TCF4 methylation between GCs and normal gastric mucosa (67.5 vs. 40.0%, respectively, by MSP and 75.8 vs. 30.0%, respectively, by PS; p < 0.05). There was significant correlation between TCF4 methylation status by PS and tumor size (p = 0.004), Lauren classification (p = 0.043), depth of invasion (p < 0.001), nodal metastasis (p = 0.021), and tumor–node–metastasis (TNM) stage (p = 0.045).

Conclusions

These results suggest that inactivation of TCF4 by promoter methylation may play a role in the early stage of gastric carcinoma progression. Furthermore, standard polymerase chain reaction followed by PS may provide a more specific and quantitative diagnostic alternative to MSP, which may be of benefit in oncology research.

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Acknowledgment

This research was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare (0720570) and a grant from the Institute of Medical System Engineering (iMSE) in the GIST, Republic of Korea.

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Authors and Affiliations

  1. Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea

    Jae Kyoon Joo MD, PhD, Sang Hyun Kim MD, Ho Gun Kim MD, PhD, Dong Yi Kim MD, PhD & Seong Yeob Ryu MD, PhD

  2. Department of Pathology, Chonnam National University Medical School, Gwangju, Korea

    Kyung Hwa Lee MD, PhD & Jae Hyuk Lee MD, PhD

Authors
  1. Jae Kyoon Joo MD, PhD
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  2. Sang Hyun Kim MD
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  3. Ho Gun Kim MD, PhD
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  4. Dong Yi Kim MD, PhD
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  5. Seong Yeob Ryu MD, PhD
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  6. Kyung Hwa Lee MD, PhD
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Correspondence to Jae Hyuk Lee MD, PhD.

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Joo, J.K., Kim, S.H., Kim, H.G. et al. CpG Methylation of Transcription Factor 4 in Gastric Carcinoma. Ann Surg Oncol 17, 3344–3353 (2010). https://doi.org/10.1245/s10434-010-1131-z

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  • DOI: https://doi.org/10.1245/s10434-010-1131-z

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