Telomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation, negatively regulates telomere length in various diseases, including cancers. Here we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones.
Relative Telomere length and subtelomeric methylation levels were assessed using monochrome multiplex qPCR and bisulfite sequencing, respectively, in different gallbladder tissue types including different grades of GBC, gallstones and adjacent non tumor.
We found telomere length to shorten significantly in overall GBC, but specifically in early grade cancer. We also found D4Z4 and DNF92 subtelomeric sequences to be hypermethylated and hypomethylated, respectively, in GBC, however, their methylation levels differed significantly, only in early grade cancer. We could not find any specific correlation between subtelomeric methylation and telomere length in GBC. Interestingly, telomere length and subtelomeric methylation differed significantly in GBC without gallstones but not in GBC with gallstones.
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This study, thus, suggests that telomere dysfunction and changes in methylation levels may occur earlier in the progression of GBC while presence of gallstones may have no effect on telomere length as well as on methylation levels. This article is protected by copyright. All rights reserved.