Lack of telomerase RNA gene hTERC expression in alternative lengthening oftelomeres cells is associated with methylation of the hTERC promoter

Citation
Sf. Hoare et al., Lack of telomerase RNA gene hTERC expression in alternative lengthening oftelomeres cells is associated with methylation of the hTERC promoter, CANCER RES, 61(1), 2001, pp. 27-32
Citations number
21
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
61
Issue
1
Year of publication
2001
Pages
27 - 32
Database
ISI
SICI code
0008-5472(20010101)61:1<27:LOTRGH>2.0.ZU;2-H
Abstract
The immortal phenotype of most human cancers is attributable to telomerase expression. However, a number of immortal cell lines and tumors achieve tel omere maintenance in the absence of telomerase via alternative mechanisms k nown as ALT (alternative lengthening of telomeres). Here we show that the p romoter of the telomerase RNA gene (hTERC) is methylated in three of five A LT cell lines and is associated with a total absence of hTERC expression in the three lines. Treatment with 5-azacytidine in combination with trichost atin A resulted in partial demethylation of the hTERC promoter and expressi on of the gene. Partial methylation was detected in tumors (5%) and in immo rtal cell lines (27%). Cell lines with partial methylation express hTERC. O nly in ALT cell lines does there appear to be a strong correlation between hTERC promoter hypermethylation and lack of hTERC expression.