hTERT Gene Amplification and Increased mRNA Expression in Central Nervous System Embryonal Tumors

Fan, Xing; Wang, Yunyue; Kratz, John Ernest; Brat, Dan J.; Robitaille, Yves; Moghrabi, T. Albert; Perlman, Elizabeth J.; Dang, Chi V.; Burger, Peter C.; Eberhart, Charles G.

doi:10.1016/s0002-9440(10)64311-8

Cited by 65 publications

(44 citation statements)

References 28 publications

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“…In FISH analysis, about half of the cases demonstrated 3 hTERT gene copies per nucleus. These data are in agreement with previous studies showing that hTERT amplification is a common finding in epithelial and brain tumors, [18][19][20] but the association between this feature and telomerase activity has not been evaluated. In our study of colorectal cancer, no significant association between hTERT gene copy number and hTERT RNA expression or telomerase activity levels could be demonstrated, indicating that this factor is of no or minor importance for the expression of telomerase in colorectal cancer.…”

Section: Discussionsupporting

confidence: 89%

“…It is fully possible that the hTERT gene copy number can be of significance in this respect for other tumors since in embryonic tumors of the central nervous system an association between hTERT amplification, studied by differential PCR, and hTERT RNA expression has been described. 20 No data on telomerase activity levels were however given. The collected data on hTERT gene copy numbers are in line with CGH analyses, showing that gene amplifications are common in colorectal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…17 Interestingly, amplification (or increase in gene copy number) of the hTERT gene at chromosome 5p15.33 has been demonstrated in a significant fraction of established cell lines and malignant tumors of different origin using FISH or differential PCR. [18][19][20] Whether this increased gene dosage also results in an increased hTERT RNA expression followed by upregulation of telomerase activity has not been clarified. In a series of embryonal brain tumors, hTERT gene amplification was associated with increased mRNA expression but telomerase activity was not studied.…”

mentioning

confidence: 99%

“…In a series of embryonal brain tumors, hTERT gene amplification was associated with increased mRNA expression but telomerase activity was not studied. 20 In our study, we analyzed a series of colorectal carcinomas for hTERT gene copy number, hTERT RNA levels, telomerase activity, p53 protein expression and DNA ploidy. Our data indicate that increased copy numbers of the hTERT gene is common in colorectal carcinoma and is associated with p53 accumulation and DNA ploidy but not with hTERT expression or telomerase activity.…”

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confidence: 99%

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hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer

Palmqvist

Zhang

et al. 2005

Intl Journal of Cancer

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In a majority of malignant human tumors telomerase activity can be detected, suggesting an immortal phenotype. Expression of the reverse transcriptase subunit, hTERT, in the human telomerase complex is required for telomerase activity. The regulation of hTERT, from gene level to a fully functional protein, is still a poorly understood process. Increased copy number of the hTERT gene has been demonstrated in a significant portion of established cell lines and tumors of different origin but its relevance for telomerase activity levels is unclear. In the present study, we examined the hTERT gene copy number using fluorescence in situ hybridization (FISH) in samples from 64 colorectal carcinomas and an increased copy number (≥ 3 hTERT gene copies/nucleus) was observed in 31 cases (48%). No statistical association existed between hTERT gene copy number and hTERT RNA expression or telomerase activity. However, a significant relationship was found between an increase in hTERT gene copy number and p53 protein accumulation (p = 0.002) and aneuploidy (p = 0.036). Only 4 tumors showed microsatellite instability, 3 of which had a normal hTERT gene copy number. The data indicated that the increased copy number of the hTERT gene in colorectal carcinoma was a result of genomic instability with no obvious consequence for telomerase activity levels. © 2005 Wiley‐Liss, Inc.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer

Palmqvist

Zhang

et al. 2005

Intl Journal of Cancer

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“…However, post-translational modifications may also contribute to the regulation of hTERT activity (Kang et al, 1999). Increased expression of hTERT resulting from gene amplification was recently reported in embryonal brain tumours (Fan et al, 2003) and cervical carcinoma (Zhang et al, 2002). The hTERT gene is located on chromosome 5p15, a chromosomal arm that is commonly overepresented or amplified in lung cancer (Luk et al, 2001).…”

mentioning

confidence: 99%

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

et al. 2006

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Telomerase reactivation is a hallmark of human carcinogenesis. Increased telomerase activity may result from gene amplification and/or overexpression. This study evaluates the prognostic value of hTERT gene amplification and mRNA overexpression in 144 resectable non-small-cell lung cancer (NSCLC) specimens. The hTERT gene copy number was assessed by quantitative polymerase chain reaction (qPCR) on laser-capture microdissected tumour cells of 81 tumours, and by fluorescence in situ hybridisation (FISH) on a subset of 59 tumours. hTERT mRNA level was determined by reverse transcription (RT) -qPCR in 130 tumours. In total, 57% of (46 out of 81) primary NSCLC specimens demonstrated hTERT amplification, which was significantly more common (Po0.001) in adenocarcinoma (30 out of 40) than in squamous cell carcinoma (13 out of 37). The hTERT mRNA overexpression was noted in 74% (94 out of 130) of tumours; it was more frequent in squamous cell than in adenocarcinoma (87 vs 68%, P ¼ 0.03). Overexpression was significantly associated with amplification (P ¼ 0.03), especially in adenocarcinoma. The hTERT gene amplification was prognostic for shorter recurrence-free survival (hazard ratio ¼ 2.16, P ¼ 0.03). These data indicate that gene amplification is an important mechanism for hTERT overexpression in lung adenocarcinoma and is an independent poor prognostic marker for disease-free survival in NSCLC.

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Embryonal Tumors

Gajjar

2010

Pediatric Hematology and Oncology

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hTERT Gene Amplification and Increased mRNA Expression in Central Nervous System Embryonal Tumors

Cited by 65 publications

References 28 publications

hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer

hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

Embryonal Tumors

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