Rearrangements of minisatellites in the human telomerase reverse transcriptase gene are not correlated with its expression in colon carcinomas.
Telomerase activation is crucial in human carcinogenesis. The limiting component of telomerase, the catalytic subunit (hTERT), is undetectable in normal somatic cells but present in most tumor cells, including the earliest stages of colon carcinoma. The mechanisms involved in the differential expression in normal and tumor cells are not understood. In normal cells hTERT expression is shut down by a repressor, and upregulation could be a consequence of cis-acting changes in the hTERT gene, making it resistant to repression. We have identified a polymorphic and a monomorphic minisatellite in the second intron of the hTERT gene, and polymorphic one in intron 6. The polymorphic minisatellite in intron 2 contains binding sites for c-Myc, which has been shown to upregulate hTERT transcription. Screening colon carcinoma DNAs for rearrangements of hTERT minisatellites we detected no changes in 33 samples from tumors, most of which express hTERT. This indicates that size rearrangements of the hTERT minisatellites are not required for telomerase expression in colon carcinomas. Minor changes and one LOH were seen in five tumors.
Szutorisz
H
H
Institute for Experimental Cancer Research, CH-1066 Epalinges, Switzerland.
Palmqvist
R
R
Roos
G
G
Stenling
R
R
Schorderet
D F
DF
Reddel
R
R
Lingner
J
J
Nabholz
M
M
D001483:Base Sequence; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D015321:Gene Rearrangement; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012313:RNA; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics*
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D004247:DNA; D019098:Telomerase