Article

Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells.

Cancer Research Unit, Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, NSW 2145 Australia, and University of Sydney, NSW 2006, Australia.
Cancer Science (impact factor: 3.33). 07/2008; 99(6):1092-9. DOI:10.1111/j.1349-7006.2008.00815.x
Source: PubMed

ABSTRACT Telomerase is a ribonucleoprotein enzyme complex that adds telomeric repeats to the ends of chromosomes. The core telomerase components are the telomerase reverse transcriptase (TERT) catalytic subunit, and the telomerase RNA (TR) template subunit. In most cancers, telomerase is expressed at levels that are substantially higher than in normal cells. A known consequence of telomerase up-regulation which is considered to play a critical role in oncogenesis is maintenance of telomere length, and thus evasion by cancer cells of the normal limits on proliferation that are associated with the steady decrease in telomere length that accompanies proliferation of normal cells. It has also been suggested that telomerase up-regulation confers other advantages on cancer cells independent of its enzymatic activity. The mechanisms responsible for up-regulation of telomerase in cancer are incompletely understood. Here we review evidence suggesting that this frequently results from increased copy number of the genes encoding telomerase components. The TERT gene is located at human chromosome band 5p15.33, and the telomerase RNA component (TERC) gene that encodes TR is at 3q26.3. Chromosomal gains and gene amplifications involving chromosome arms 5p and 3q are among the most frequent in human tumors. Increased TERT and TERC gene dosage has been detected frequently in a variety of human cancers, and clonal evolution of cells with increased TERT or TERC copy number has been observed, suggesting a growth advantage in cells with increased TERT or TERC gene dosage.

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Keywords

accompanies proliferation
 
cancer cells
 
cancer cells independent
 
cancers
 
chromosome arms 5p
 
core telomerase components
 
encodes TR
 
enzymatic activity
 
gene amplifications
 
genes encoding telomerase components
 
human cancers
 
human chromosome band 5p15.33
 
human tumors
 
Increased TERT
 
mechanisms responsible
 
ribonucleoprotein enzyme complex
 
telomerase reverse transcriptase
 
telomerase RNA component
 
TERC copy number
 
TERC gene dosage