CpG methylation of transcription factor 4 in gastric carcinoma.
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.
Joo
Jae Kyoon
JK
Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
Kim
Sang Hyun
SH
Kim
Ho Gun
HG
Kim
Dong Yi
DY
Ryu
Seong Yeob
SY
Lee
Kyung Hwa
KH
Lee
Jae Hyuk
JH
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors