Promoter hypermethylation of RASSF1A in esophageal squamous cell carcinoma.
OBJECTIVE
The RAS association domain family 1A (RASSF1A) gene, a candidate tumor suppressor gene, is frequently inactivated by hypermethylation of its promoter region in several human cancers. The aim of this study was to evaluate the promoter methylation status of the RASSF1A in esophageal squamous cell carcinoma.


METHODS
We analyzed the methylation status of RASSF1A promoter by methylation-specific PCR in 23 esophageal squamous cell carcinoma cell lines and 48 primary tumors.


RESULTS
Hypermethylation of RASSF1A was found in 74% of cell lines and 52% of primary tumors. The presence of hypermethylation was statistically associated with loss of RASSF1A mRNA expression in both cell lines (P = 0.007) and primary tumors (P = 0.003). There was a statistically significant correlation between the presence of hypermethylation and tumor stage (P = 0.009).


CONCLUSIONS
Our findings suggest that epigenetic silencing of RASSF1A gene expression by promoter hypermethylation could play an important role in primary esophageal squamous cell carcinogenesis.
Kuroki
Tamotsu
T
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, Pennsylvania 19107, USA.
Trapasso
Francesco
F
Yendamuri
Sai
S
Matsuyama
Ayumi
A
Alder
Hansjuerg
H
Mori
Masaki
M
Croce
Carlo M
CM
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; C411762:RASSF1 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D012313:RNA; D004247:DNA