Frequent gain of the human telomerase gene TERC at 3q26 in cervical adenocarcinomas

Andersson, Sonia; Kl, Wallin; Hellström, Ann‐Cathrin; Le, Morrison; Hjerpe, Anders; Auer, Gert; Ried, Thomas; Larsson, Catharina; Heselmeyer‐Haddad, Kerstin

doi:10.1038/sj.bjc.6603253

Cited by 46 publications

(39 citation statements)

References 36 publications

(43 reference statements)

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“…observed in various tumors (38)(39)(40), and it may be one mechanism of increased hTR expression in the tumors. More recently, a viral form of telomerase RNA (vTR) with 88% homology to chicken telomerase RNA was found to be encoded by oncogenic strains of Marek's disease virus (MDV) but not by nononcogenic MDV strains (41).…”

Section: Discussionmentioning

confidence: 99%

Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels

et al. 2008

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Activation of telomerase is a crucial step during cellular immortalization, and in some tumors this results from amplification of the human telomerase reverse transcriptase (hTERT) gene. Immortalization of normal human cells has been achieved by transduction with hTERT cDNA under the control of a strong heterologous enhancer/promoter, but this is sometimes an inefficient process, with periods of poor growth or even crisis occurring before immortalization. Here, we showed that normal human mammary epithelial cells expressing exogenous hTERT amplified the transgene extensively and expressed high levels of hTERT mRNA and protein. Paradoxically, the cells had low levels of telomerase activity and very short telomeres, indicating that telomerase activity did not correlate with hTERT expression. These cells contained only f20 human telomerase RNA (hTR) molecules/cell (compared with f120 hTR molecules per 293 cell). Expression of exogenous hTR caused increased telomerase activity and telomere lengthening. These data indicate that some hTERTtransduced normal cells may express high levels of the transgene but fail to up-regulate endogenous hTR expression sufficiently to enable expression of robust levels of telomerase activity. [Cancer Res 2008;68(9):3115-23]

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Section: Discussionmentioning

confidence: 99%

Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels

et al. 2008

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“…We are aware that our study had some limitations, such as the small number of cases. To obviate this drawback, further prospective investigations with long-term follow-up will be necessary, in view of the possible introduction of hTERC FISH analysis into decision-making algorithms [44,45,46,47,48,49,50]. …”

Section: Discussionmentioning

confidence: 99%

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Zappacosta

Ianieri²,

Buca³

et al. 2015

Acta Cytologica

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Objective: This study was designed to evaluate whether the adjunct of human telomerase RNA component (hTERC) fluorescence in situ hybridization (FISH) analysis to cytological diagnosis and human papillomavirus (HPV)-DNA testing may serve as a predictive marker for distinguishing cervical lesions destined to regress from those at high risk of progression towards invasive cancer. Study Design: hTERC FISH analysis was performed on 54 residual liquid-based cytology specimens obtained from women referred to colposcopy for the detection of atypical squamous cells of undetermined significance or worse (ASCUS+) lesions. Histological diagnosis was considered the gold standard and cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) as the worst outcome. Results: Oncogenic HPV-DNA was found in 96.3% of the specimens. Among these, 38.5% revealed a CIN2+ diagnosis. hTERC gene amplification was detected in 37% of the cases; among these, 70% showed up as CIN2+. hTERC FISH analysis significantly improves the specificity and positive predictive value of HPV-DNA testing, thus differentiating patients with a CIN2+ diagnosis from those with a CIN2- diagnosis. Conclusions: Despite the limitation of a small study sample, our findings provide promising data, indicating the possible role of hTERC analysis in the assessment of the risk of developing cervical cancer. This approach would implement the specificity of DNA testing, avoiding overtreatment at the same time. Prospective follow-up studies are needed with the aim of introducing hTERC FISH into decision-making algorithms.

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“…In other recent finding in different grouping of laryngeal lesions produced by Liu et al, (2012) they stated a significant elevated percentage of amplified TERC gene in moderate dysplasia, severe dysplasia, carcinoma in situ and invasive carcinoma compared to normal epithelium and mild dysplasia (p<0.0001). Moreover, Andersson et al, (2006) showed TERC gene amplification in cervical adenocarcinomas with absolute mean copy number ranged between 2.3 and 5.2 comparable to the mean of cervical adenocarcinomas without infection of human papillomavirus (HPV was 3.3). It has to be taken into account that all these mentioned TERC gene amplification studies were done in the solid tumours.…”

Section: Discussionmentioning

confidence: 99%

Low Level of TERC Gene Amplification between Chronic Myeloid Leukaemia Patients Resistant and Respond to Imatinib Mesylate Treatment

Ashari

Sulong

Hassan

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Frequent gain of the human telomerase gene TERC at 3q26 in cervical adenocarcinomas

Cited by 46 publications

References 36 publications

Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels

Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Low Level of TERC Gene Amplification between Chronic Myeloid Leukaemia Patients Resistant and Respond to Imatinib Mesylate Treatment

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