Increased hTR expression during transition from adenoma to carcinoma is not associated with promoter methylation.

ABSTRACT

Human telomerase RNA component (hTR) expression, which increases in the majority of cancer cells with an acquisition of telomerase activity, was concomitantly evaluated with methylation status and human telomerase reverse transcriptase (hTERT) expression in colorectal cancers and precursor lesions. hTR and hTERT expressions were detected by in situ hybridization and reverse transcription following polymerase chain reaction, respectively, in 15 colonic adenomas, 19 sporadic colonic cancers at various histological stages, and 3 normal colonic mucosa samples. The methylationstatus of hTR was evaluated by methylation-specific polymerase chain reaction following restriction endonuclease digestion and direct sequencing. hTERT expression was detected in 16 of 19 cancers. hTR expression was detected in all cancers including two cases of intramucosal carcinoma. No hTR signals were detected in the normal epithelium or in the adenomas with severe atypism. CpG dinucleotides in the 5'-untranslated region of hTR were completely unmethylated from -204 to -3 and mosaically methylated from -290 to -272, irrespective of the atypism. These results suggest that hTR expression is increased at the adenoma-to-carcinoma transition stage but is not always associated with hTERT expression. Hypomethylation of the hTR promoter region is not likely to be the main mechanism regulating hTR expression.