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      Human telomerase RNA component (hTERC) gene amplification detected by FISH in precancerous lesions and carcinoma of the larynx

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          Abstract

          Background

          Gain of 3q26 is frequently observed in squamous cell carcinomas of mucosal origin, including those originating in the head and neck region. The human telomerase RNA component (hTERC) gene, which is located on chromosome 3q26, encodes for an RNA subunit of telomerase that maintains the length of telomeres through cellular divisions, and is activated in malignant diseases. The present study was designed to detect hTERC amplification in laryngeal lesions and evaluate whether this might serve as a supportive biomarker in histopathological analysis for in the diagnosis of laryngeal lesions.

          Methods

          Fluorescent in situ hybridization (FISH) was applied on formalin-fixed paraffin-embedded blocks of 93 laryngeal specimens, including 14 normal epithelium (NE), 15 mild dysplasia (Md), 18 moderate dysplasia (MD), 16 severe dysplasia (SD), 9 carcinoma in situ (CIS), and 21 invasive carcinoma (IC)).

          Results

          By histopathologic examination, hTERC amplification rates in NE, Md, MD, SD, CIS and IC cases were 0% (0/14), 13.33% (2/15), 72.22% (13/18), 81.25% (13/16), 100% (9/9) and 100% (21/21), respectively. Amplification of hTERC was significantly associated with histopathologic diagnosis (P < 0.0001). The percentage of hTERC amplification in patients with MD, SD, CIS, and IC was significantly higher than those with NE or Md (P < 0.0001). The number of cells with abnormal signals increased and the abnormal signal patterns were diversified with increasing severity of laryngeal dysplasia (P < 0.0001).

          Conclusions

          The hTERC amplification is important in the development of laryngeal squamous cell carcinoma (LSCC). FISH detection of hTERC amplification may provide an effective approach in conjunction with histopathologic evaluation for differential diagnosis of laryngeal lesions.

          Virtual Slides

          The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2226606266791985

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          Most cited references27

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          Protein composition of catalytically active human telomerase from immortal cells.

          Scott B Cohen, Mark E Graham, George O. Lovrecz … (2007)
          Telomerase is a ribonucleoprotein enzyme complex that adds 5'-TTAGGG-3' repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for approximately 90% of human cancers. We have purified human telomerase approximately 10(8)-fold, with the final elution dependent on the enzyme's ability to catalyze nucleotide addition onto a DNA oligonucleotide of telomeric sequence, thereby providing specificity for catalytically active telomerase. Mass spectrometric sequencing of the protein components and molecular size determination indicated an enzyme composition of two molecules each of telomerase reverse transcriptase, telomerase RNA, and dyskerin.
          Article 0 comments Cited 171 times – based on 0 reviews     Review now
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            Focus on head and neck cancer.

            Li Mao, Waun Hong, Vassiliki Papadimitrakopoulou (2004)
            Article 0 comments Cited 71 times – based on 0 reviews     Review now
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              Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells.

              Ying Cao, Tracy Bryan, Roger R. Reddel (2008)
              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.
              Article 0 comments Cited 59 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Diagn Pathol
                Journal ID (iso-abbrev): Diagn Pathol
                Title: Diagnostic Pathology
                Publisher: BioMed Central
                ISSN (Electronic): 1746-1596
                Publication date Collection: 2012
                Publication date (Electronic): 30 March 2012
                Volume: 7
                Page: 34
                Affiliations
                [1 ]Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
                [2 ]Department of Pathology, Capital Medical University, Beijing, 100069, China
                Article
                Publisher ID: 1746-1596-7-34
                DOI: 10.1186/1746-1596-7-34
                PMC ID: 3359179
                PubMed ID: 22463766
                SO-VID: 548f4223-ab93-4e87-883f-51c21b00fce6
                Copyright © Copyright ©2012 Liu et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 25 January 2012
                Date accepted : 30 March 2012
                Categories
                Subject: Research

                ScienceOpen disciplines: Pathology
                Keywords: human telomerase rna component gene,laryngeal carcinoma,amplification,fluorescent in situ hybridization
                Data availability:
                ScienceOpen disciplines: Pathology
                Keywords: human telomerase rna component gene, laryngeal carcinoma, amplification, fluorescent in situ hybridization

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