Hypomethylation in the promoter region of POMC gene correlates with ectopic overexpression in thymic carcinoids.
The ectopic ACTH syndrome is caused by abnormal expression of the POMC gene product arising from non-pituitary tumors in response to the ectopic activation of the pituitary-specific promoter of this gene. It has been proved that methylation of the CpG island in the promoter region is associated with silencing of some genes. Using bisulphite sequencing, we identified hypermethylation in the 5' promoter region of the POMC gene in three normal thymuses and one large cell lung cancer, and hypomethylation in five thymic carcinoid tumors resected from patients with ectopic ACTH syndrome. The region undergoing hypermethylation was narrowed to coordinates -417 to -260 of the POMC promoter. Furthermore, we observed that the levels of POMC expression correlated with the methylation density at -417 to -260 bp across the E2 transcription factor binding region of the POMC promoter. It is concluded that hypomethylation of the POMC promoter in thymic carcinoids correlates with POMC overexpression and the ectopic ACTH syndrome.
Ye
Lei
L
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Second Medical University, 197 Ruijin Er Lu, Shanghai 200025, People's Republic of China.
Li
Xiaoying
X
Kong
Xiangyin
X
Wang
Weiqing
W
Bi
Yufang
Y
Hu
Landian
L
Cui
Bin
B
Li
Xi
X
Ning
Guang
G
D000182:ACTH Syndrome, Ectopic / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013953:Thymus Neoplasms / Q000378:metabolism*
D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin