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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2010

01-12-2010 | Gastrointestinal Oncology

CpG Methylation of Transcription Factor 4 in Gastric Carcinoma

Authors: Jae Kyoon Joo, MD, PhD, Sang Hyun Kim, MD, Ho Gun Kim, MD, PhD, Dong Yi Kim, MD, PhD, Seong Yeob Ryu, MD, PhD, Kyung Hwa Lee, MD, PhD, Jae Hyuk Lee, MD, PhD

Published in: Annals of Surgical Oncology | Issue 12/2010

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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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Metadata
Title
CpG Methylation of Transcription Factor 4 in Gastric Carcinoma
Authors
Jae Kyoon Joo, MD, PhD
Sang Hyun Kim, MD
Ho Gun Kim, MD, PhD
Dong Yi Kim, MD, PhD
Seong Yeob Ryu, MD, PhD
Kyung Hwa Lee, MD, PhD
Jae Hyuk Lee, MD, PhD
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1131-z

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