Telomerase is important in cancer biology, improving the division capacity of cancer cells. Division of molecular and cardiovascular biology, cincinnati childrens. The analysis of telomerase activity status has potential clinical utility for diagnosis, screening and monitoring treatment. Current tissue molecular markers in colorectal cancer. Progress during the last year has revealed the threedimensional architecture of both human and ciliate telomerase at about 25 a resolution, obtained using single particle electron microscopy em. Telomerase has been detected in a majority of human malignant tumors, making telomerase activity ta one key difference between mortal and immortal cells. Jun 10, 2019 finally, a random forest classifier integrating telomerase associated multiomics signatures identifies two cancer subtypes showed profound differences in telomerase activity and patient survival. Telomerase activity evaluation has undergone an improvement in its methodology. The activation of telomerase, the enzyme necessary to extend chromosome ends telomeres is the key step in cell immortalization. Telomerase gene therapy ameliorates the effects of. The first way of intervening in telomerase action in human cancer cells exploited the fact that the telomeric dna makes the molecular scaffold for the binding of telomereprotective proteins, which include dna sequencespecific binding proteins. For the first time we have also shown the ability of telomerase to detect micro and probably occult metastasis in gynecological malignancies. In the future, telomerase measurements, in conjunction with other molecular markers, may have utility in the early diagnosis of breast cancer.
Telomerase rna as a detection marker in the serum of breast. Despite this divergence in identity among telomerase associated proteins, the biological roles of holoenzyme proteins have some similarity. Telomerase inhibitors in the treatment of cancer are awaited with great anticipation. Telomerase a potential molecular marker of lung and cervical cancer article in clinical chemistry and laboratory medicine 4010. Basic scientists and clinicians must work together if this strategy is to mature. Rna has also been found circulating in the plasma of normal subjects and cancer patients. Telomerase gene therapy in adult and old mice delays aging. With the advent of molecular diagnostics, in which small amounts of clinical samples can be analyzed by molecular analysis, the possibility of improving fnabased characterization of thyroid nodules is possible.
The absence of telomerase activity in cervical scrapes from healthy women indicated the potential of telomerase to serve as a good screening marker for the early diagnosis of cervical cancer. Clinical importance of molecular markers of adult diffuse. Telomerase is a reverse transcriptase enzyme that carries its own rna molecule e. The aim of this study was to investigate the role of testing telomerase activity in pancreatic endocrine tumours. Although upregulated telomerase activity is closely linked to the cellular immortality characteristic of late stage carcinogenesis, recently, mutations in the telomerase rna gene in humans have been associated with dyskeratosis congenita and aplastic anemia, both typified by impaired haemopoietic function. Thus the level of telomerase activity in tissue specimens may depend on the number of tumor cells in a specimen. In particular, telomerase reexpression in a telomerasedeficient mouse model with short telomeres, resulted in a larger brain weight, a thicker myelin sheath, better performance in an innate avoidance test as a measure of the health of the olfactory bulb, and increased molecular. Request pdf telomerase molecular marker in blood of ovarian cancer patients studies conducted in last 10 years suggest diagnostic and prognostic significance of circulating tumour cells ctc. Further examinations will prove the feasibility of the detection of htert mrna in blood. The telomerase reverse transcriptase has an essential role in telomere maintenance and in cancer biology. Pdf222 download pdf of article text and main figures. In other types in which telomerase becomes upregulated according to tumor progression, it is a useful prognostic indicator.
Molecular markers in fine needle aspirates of the thyroid. Telomeres and telomerase in heart ontogenesis, aging and. However, telomerase activity is known to be upregulated in the activated lymphocytes in the patients with special types of inflammation such as autoimmune diseases. Aims telomerase activation is known to be a common event in human cancer and may be a useful marker for malignancy. The importance of the who 2016 update is that key molecular markers have now become integral to the classification of glial tumours. The detection of circulating tumor cells and micrometastases may have important therapeutic and prognostic implications. The telomeric constitution includes three known entities. Telomerase is an enzyme that immortalizes cells by maintaining a constant telomere length.
Statistical analysis on the relationship between htert positivity in noncancerous epithelia and subsequent lung cancer development was carried out using fishers exact test. A new molecular marker for parathyroid carcinoma article pdf available in biochemical and biophysical research communications 2651. A molecular marker is a dna sequence in the genome which can be located and identified. Telomerase expression in noncancerous bronchial epithelia is.
The association of telomere length and genetic variation in telomere. Telomerasea molecular marker for cervical cancer screening. Detailed molecular functions of recql5 are not clear. As a result of genetic alterations mutations, insertions, deletions, the base composition at a particular location of the genome may be different in different plants. Telomere length measurement by quantitative realtime pcr. However, telomere length measurements in tumour tissue, either from surgical specimens or specimens taken at the time of biopsy, or from other bodily fluids may serve as a molecular marker for risk assessment, prediction for response to therapy e. Aging is a process that affects most living organisms, involving the progressive decline of cellular function that ultimately leads to. Jan 11, 20 telomerase replenishes the telomere cap of the dna 12. Human telomeres are repetitive sequences of the ttaggg motif, located at the very ends of chromosomes 24, 25. The finding of telomerase activity in some histologically normal mucosa was unexpected. Telomerase activity seems to play a role in the development and pathogenesis of thyroid carcinoma. Telomeres are repeated sequences found at the end of the linear chromosomes of most eukaryotes and are required for chromosome integrity. Telomerase results to be active in human germ, stem cells, several malignant cell tumors and in immortal ized cell lines.
The entire aging process cannot be explained solely by telomere shortening. Applications of telomerase research in the fight against. Telomerase as a prognostic marker and therapeutic target in. In cellular biology, the role of telomerase is of growing complexity. Telomerase protein expression was evaluated as positive when nuclear staining was confirmed by two molecular oncologists, in a blinded manner by one and confirmed by another.
Molecular detection of telomerasepositive circulating. Telomerase molecular marker in blood of ovarian cancer. Its incidence of expression and its application as a tumor marker remain to be elucidated. Analyzing the expression level of htert and hterc genes encoding telomerase and telomere length measurement may constitute new markers. Molecular markers and marker assisted breeding in plants. Telomerase activity is responsible for cell immortality.
Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Quantitative evaluation of telomerase activity in voided urine represents a molecular test for early diagnosis of bladder tumor. Pdf diagnostic value of urinary molecular markers in. Telomerase activity as a diagnostic marker in cancer. Broken chromosome ends, lacking telomeres, show a propensity to fuse with each other and are also susceptible to degradation by exonucleases. Furthermore, investigations into the biology of telomerase have revealed important clues into the causes of cell death and have made progress toward answering one of the most. Telomerase activity and telomerase subunits gene expression.
In addition, the results suggest that the c250t htert promoter mutation and telomere length assessment may serve as important molecular markers of hnscc progression. Problems of telomerase activity measurement and modulation by enzyme inhibitors or activs well. Molecular staging using markers such as telomerase activity in combination with other molecular markers may be particularly useful in this regard. Shay 1, 2 1 department of cell biology, the university of texas southwestern medical center, dallas, texas. Using a quantitative realtime pcr assay, we show that nonhomologous end joining between a telomere and an inducible dsb was undetectable in wildtype cells, but occurred within a few hours of dsb induction in. Even urinary telomerase could be a potentially useful urinary tumor marker. Telomerase is also called terminal transferase, is a ribonucleoprotein that adds a speciesdependent telomere repeat sequence to the 3 end of telomeres. Forcing telomerase to make mutant telomeric dna in cancer cells. Bladder cancer is the second most common genitourinary malignancy in the united states. Recently, there is an increasing amount of experimental data regarding detection of telomerase activity andor htert expression for diagnosis of various cancers in cells obtained from clinical materials such as fluid, secretion, washes, brushings, blood, and fine needle aspirates. Role of telomeres and telomerase in aging and cancer jerry w. Selective breeding of these mice produced successive generations with signs of premature aging and shortened life spans, providing further evidence of the role of telomeres and telomerase in aging. Here, we set out to assess the prognostic value of biomarkers indicating telomerase or alt activation in patients with neuroblastoma and to examine the potential relevance of telomerase as a molecular target in this malignancy. Shroyer, michael frost, raihanatou diallo, franz fogt, karlludwig scha.
Telomerase activity, cell proliferation, and cancer. Other authors have demonstrated that a combination of 3 molecular markers idhmut, telomerase promoter mutations tertpmut, and 1p19q codeletions can be used to categorize lowergrade gliomas and glioblastomas gbms into clinically relevant molecular subsets. Pancancer analysis identifies telomeraseassociated. Therefore, molecular markers in this article are mainly referred to as dna markers except specific definitions are given, although isozymes and protein markers are al. Thus, telomerase is a useful marker for cancer diagnosis and in some instance as a prognostic indicator of outcome. Telomeres and telomerase group, molecular oncology program, spanish national cancer centre cnio, madrid, spain. Here, telomerase activity in bladder washes was analyzed and compared with the final pathological diagnosis in 23 patients with bladder transitional cell carcinoma tcc. Telomeres play a central role in cell fate and aging by adjusting the cellular. The objective of this policy is to evaluate whether testing for molecular markers in fine needle aspirates of the thyroid improves the net health outcome in individuals with thyroid nodules with an indeterminate finding on the fine needle aspirate. Telomerase the enzyme responsible for protecting chromosome ends from shortening during dna replication to avoid potentially catastrophic dna lossis an rnp composed of the telomerase reverse transcriptase tert protein and the telomerase rna tr among other constituents. On the basis of our results, the trap assay may be clinically useful in providing a rapid diagnosis of malignancy in cats. Pdf telomeres of most eucaryotes terminate in long stretches of short. Expression of the reversetranscriptase telomerase allows for extension of telomeric repeats to counteract natural telomere shortening. Molecular genetics of telomeres and telomerase department.
Telomerase activity as a marker for malignancy in feline tissues. Telomerase activity is known to be absent in most human somatic cells, as an effect of which telomere shortening is known to occur and thus poses a barrier to tumor growth and marks a molecular path towards aging. Telomerase activity in primary and secondary glioblastomas. In general, the histological features of pancreatic endocrine tumours cannot be used to determine their malignant potential. Amplification of telomerase htert gene is a poor prognostic marker in nonsmallcell lung cancer skip to main content thank you for visiting.
This type of analysis presents some difficulties for measurement of telomerase activity in a clinical laboratory setting. Molecular markers and markerassisted breeding in plants. Telomeres are repetitive nucleotide sequences located at the termini of linear chromosomes of most eukaryotic organisms. In conclusion, telomerase is activated in oral squamous cell carcinoma, supporting the concept that it is an important factor in tumorigenesis. Because telomerase activity is the most general molecular marker for the identification of human cancer, the analysis of telomerase mrna expression in serum is attractive as a potential tumor marker. The large size of human telomerase rna and its molecular mass 300 kda suggest that the human telomerase enzyme complex has more than two protein subunits. Telomeres protect chromosome ends from fusing to doublestranded breaks dsbs.
Realtime quantification in plasma of human telomerase. Comparative analyses of various screening methods for the diagnosis of bladder cancer have shown that telomerase has the highest combination of sensitivity and specificity with respect to urine cytology and other biochemical marker determinations 4,6,7,2429. A new molecular marker for parathyroid carcinoma sciencedirect. Molecular characterization of chlamydomonas reinhardtii. Telomerase, considered a hallmark of cancer phatak and burger, 2007, is repressed in almost all human somatic cells but is activated in more than 90% of cancer cells. Detection of telomerase activity in different cancer. Although chlamydomonas reinhardtii, a photosynthetic unicellular green alga, is widely used as a model organism in. Use of telomerase promoter mutations to mark specific. Telomerase is a prognostic marker of poor outcome and a. Telomerase is a highly sensitive and specific molecular.
The telomerase proteins seem to have structural importance by binding dntps deoxynucleoside triphosphates or. Impact of modulation of telomerase and cancer stem. We tested feline samples to determine whether similar patterns of telomerase activity exist. This test shows a high accuracy, mainly in males bladder tumor, and could be an important non invasive diagnostic tool for bladder cancer detection in. Telomerase a ribonucleoprotein that is involved in telomere maintenance represents a promising molecular marker for cancer. It has a mw of about 500 kda 45 and contains one tert subunit, a small ter subunit 159 nucleotides versus 451 nucleotides in humans. Since telomerase is expressed almost exclusively in cancer cells, the detection of htert mrna will become a powerful marker for detection of cancer cells also in blood.
A molecular switch underlies a human telomerase disease pnas. Dna cut with styi was used as a molecular weight marker. Telomerase activity has also been analysed as a molecular marker for cancer generally by the telomerase repeat amplification protocol in, for example, fineneedle aspirates from patients with breast carcinoma, bronchial washings from patients with lung cancer, and even the blood of patients with metastatic breast cancer. A molecular marker or biomarker is a molecule able to be detected in tissue or serum and that allows identifying a particular condition or a disease. Telomerase, an enzyme that confers immortality upon cells and that is active in the majority of human tumors, has emerged as a powerful new marker and potential prognostic indicator and therapeutic target for cancer. Bladder washes and normal tissues were obtained from each patient prior to transurethral resection of bladder tumor. Established molecular markers such as mycn copy number and loss of heterozygosity for chromosome 1p3236 may help in predicting poor outcome in all age. The telomerase enzyme may also serve as a therapeutic target in feline tumors. Molecular markers a tool for exploring genetic diversity. The main markers, now routinely tested in clinical practice, are isocitrate dehydrogenase idh gene mutations mutated or wild type and codeletion of 1p19q codeleted or intact. At the molecular level, telomerase holoenzyme proteins differ between ciliates, vertebrates, and yeasts. In genetic diversity studies, the most frequently used markers are microsatellites. In summary, our results depict a telomerase associated molecular landscape in cancers and provide therapeutic opportunities for cancer treatment. Its mrna levels htert correlate with its activity and were suggested as a marker for cancer detection and progression shay and wright.
Telomerase activity as a potential diagnostic marker for. Role of telomeres and telomerase in aging and cancer. Despite this divergence in identity among telomeraseassociated proteins, the biological roles of holoenzyme proteins have some similarity. Finally, a random forest classifier integrating telomerase associated multiomics signatures identifies two cancer subtypes showed profound differences in telomerase activity and patient survival. Telomerase is a hallmark of cancer and is absent from normal epithelial cells. To examine the role of telomerase in the carcinogenesis of human glioblastomas multiforme gbms, the authors studied telomerase activity, telomerase component expression, and telomere lengths in 42 gbm samples. Its name is derived from the greek nouns telos end and mer. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. Department of molecular biology, university of california, berkeley, ca 94720, u. Telomerase as a prognostic marker and therapeutic target. Dna markers are also called molecular markers in many cases and play a major role in mo. Mas in plants 18 molecular markers and their applications in cereals breeding viktor korzun lochowpetkus gmbh, grimsehlstr. This test shows a high accuracy, mainly in males bladder tumor, and could be an important non invasive diagnostic tool for bladder cancer detection in highrisk groups screening programs.
Tyrosinase mrna has been extracted from the serum of. Pdf telomerase activity in plant cells researchgate. Telomerase and cancer human molecular genetics oxford. The progress made in molecular plant breeding, genetics, genomic selection. Tumorderived circulating dna has been found in the plasma of cancer patients. Highly recurrent point mutations in the human telomerase reverse transcriptase htert promoter have recently been reported in a number of human neoplasms. Telomerase is active in gametes and most cancer cells, but is normally absent from, or at very low levels in, most somatic cells. Introduction head and neck squamous cell carcinoma hnscc is the sixth most common cancer worldwide, representing over half a million incidents every year 1, 2. Telomeres and telomerase during human papillomavirus. Chapter 2 molecular markers of thyroid nodules sciencedirect.
The telomerase proteins seem to have structural importance by binding dntps deoxynucleoside triphosphates or dna sequences. This enzyme is required for cellular immortalization, and is. Telomerase activity is a useful cancercell detecting marker in some types of cancers in which almost all cases show telomerase activation. Detection of human telomerase reverse transcriptase htert. In contrast to the human telomerase complex, the affinitypurified telomerase from tetrahymena is monomeric 16 and is known to function as a monomer. Further study to correlate surgical margins with patient outcome is clearly needed. Telomerase is the enzyme responsible for maintenance of telomeric entity which is an rna dependent dna polymerase.
Alterations include decreased strand stability, mutations of oncogenes or of tumor suppressor genes, microsatellite alterations, and hypermethylation of several genes. Biomarkers have a high prognostic and predictive value and are an important instrument for the early diagnosis. Colorectal cancer crc is the third most common cancer worldwide. In conclusion, our data show that the purified human telomerase is active and that both the goverhang bound and unbound telomerase complexes have a molecular weight consistent with that of a dimer consisting of two htert 127 kda and two hter 153 kda subunits, as well as the two accessory proteins nop10 7. In this study, we evaluated in blindtrial fashion the association of ta with cytologic and final clinicalpathologic diagnosis in fineneedle aspirates fnas of breast lesions. The aim of this study was to use telomerase activity as a molecular marker for the detection of cancer cells in blood of patients with breast cancer. Molecular characterization of chlamydomonas reinhardtii telomeres. Urine telomerase for diagnosis and surveillance of bladder. More work is needed to explore the role of genetic variants in telomere length regulation. Apr 01, 2001 telomerase activity was detected in both of these tissues data not shown but there was considerably more activity in the advanced cancer compared to the dcis.
Telomerase activity as a potential diagnostic marker in cancer. It remains to be clearly elucidated whether quantitative differences of telomerase activity in bladder tissues and exfoliated cells can improve the clinical relevance of this molecular marker. Telomerase as a prognostic marker and therapeutic target in paediatric ependymoma mark steven barszczyk master of science laboratory medicine and pathobiology university of toronto 20 abstract paediatric ependymomas are the third most common childhood brain cancer and represent a prognostic and therapeutic challenge. Pdf telomere length measurement by quantitative realtime. Telomerase instability paves a molecular path towards cancer. Telomerase a potential molecular marker of lung and. Molecular genetics of telomeres and telomerase telomeres are the terminal proteindna complexes of linear eukaryotic chromosomes, and are essential to ensure chromosome integrity and stability. Telomerase is an independent prognostic marker of overall.