Frequent amplification of the telomerase reverse transcriptase gene in human tumors.
Activation of telomerase is a crucial step during cellular immortalization and malignant transformation of human cells and requires the induction of the catalytic component, human telomerase reverse transcriptase (hTERT), encoded by the hTERT gene. It is poorly understood how the hTERT gene is activated in human cancer cells. In the present study, we examined the hTERT gene copy number in human cancer cell lines and in primary tumor tissues. Amplification of the hTERT gene was observed in 8 of 26 (31%) tumor cell lines and 17 of 58 (30%) primary tumors examined (8 of 21 lung tumors, 3 of 10 cervical tumors, 5 of 19 breast carcinomas, and 1 of 8 neuroblastomas). In addition, 13 of 26 (50%) cell lines and 13 of 58 (22%) primary tumors displayed gain of hTERT gene copies with 3-4 copies/cell. The present findings imply that the hTERT locus may be a frequent target for amplification during tumorigenesis and that this genetic event probably contributes to the dysregulation of telomerase activity occurring in human tumors.
Zhang
A
A
Department of Oncology and Pathology, Karolinska Hospital and Institutet, Stockholm, Sweden.
Zheng
C
C
Lindvall
C
C
Hou
M
M
Ekedahl
J
J
Lewensohn
R
R
Yan
Z
Z
Yang
X
X
Henriksson
M
M
Blennow
E
E
Nordenskjöld
M
M
Zetterberg
A
A
Björkholm
M
M
Gruber
A
A
Xu
D
D
D020134:Catalytic Domain; D004268:DNA-Binding Proteins; D005784:Gene Amplification; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000502:physiology; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D012313:RNA; D019098:Telomerase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase