Hypermethylation of the CpG island of connexin 32, a candiate tumor suppressor gene in renal cell carcinomas from hemodialysis patients.
Long duration of patients on hemodialysis is a large risk for the development of renal cell carcinoma (RCC) compared to general patients. However, the carcinogenic process is still unclear. On the other hand, we have reported that connexin (Cx) 32, a molecule of gap junction, is a new tumor suppressor gene in human RCC. In this study, we investigated the clinical significance of methylation-dependent silencing of Cx32 gene in the development of the RCC from the hemodialysis patients. As the result, we found that the inactivation of Cx32 through hypermethylation of the promoter regions frequently occurred in non-cancerous regions as well as cancerous regions of kidneys from hemodialysis patients. However, the hypermethylation of Cx32 occurred only in cancerous regions but not non-cancerous regions of kidneys from the general patients without hemodialysis. Furthermore, the hypermethylation of RASSAF1A, a representative tumor suppressor gene in human RCC, occurred in cancerous regions but not non-cancerous regions of kidneys from the hemodialysis and general patients. These results suggest that Cx32 is a promising tumor suppressor gene relating to the early stage of renal carcinogenesis in the hemodialysis patients.
Yano
Tomohiro
T
Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan. yano@nih.go.jp
Ito
Fumio
F
Kobayashi
Kaori
K
Yonezawa
Yuko
Y
Suzuki
Kazuyuki
K
Asano
Ryuji
R
Hagiwara
Kiyokazu
K
Nakazawa
Hayakazu
H
Toma
Hiroshi
H
Yamasaki
Hiroshi
H
D002292:Carcinoma, Renal Cell / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D006435:Renal Dialysis; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D025521:Tumor Suppressor Proteins; D000097002:Gap Junction beta-1 Protein; C411762:RASSF1 protein, human