Tert

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 23.11.2022

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Definition
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Acronym for "telomerase reverse transcriptase" Specific DNA polymerase , an enzyme whose function is the conservation of telomeres. TERT is a ribonucleoprotein (RNP) that uses part of its RNA component as a template for "telomere repeat DNA synthesis".

General information
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The shortening of telomeres, the protein-DNA structures located at the ends of chromosomes, is considered to explain cell aging. The length and integrity of telomeres are directly related to a cell's entry into a "senescence" stage. The ability of a cell to maintain (or increase) telomere length may allow it to escape senescence.

Telomerase reverse transcriptase is active in normal body cells, but also in various tumors. Mutations in the telomerase gene lead to increased activity of the enzyme. Other gene mutations can affect the so-called promoter region ( switch region) of the telomerase gene. This creates binding sites for proteins that activate the gene excessively. The consequence is an increased production of telomerase. The cells thus attain "immortality".

Hereditary TERT mutations are detected in familial malignant melanoma. In sporadic malignant melanoma, somatic mutations in the telomerase promoter region have also been found in a smaller proportion of primary tumors but in >80% of metastases (making them more common than the BRAF mutation). Such changes also occur in the wake of sun exposure (see also keratosis actinica) and also lead to excessive telomerase activity.

These observations could enable new oncological therapeutic approaches (e.g. by using oncolytic viruses).

Literature
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  1. Cowan M et al (2016) Detection of TERT promoter mutations in primary adenocarcinoma of the urinary bladder. Hum Pathol doi: 10.1016/j.humpath.2016.02.009.
  2. Kurtis B et al (2016) Recurrent TERT promoter mutations in urothelial carcinoma and potential clinical applications. Ann Diagn Pathol 21:7-11.
  3. Macerola E et al (2015) Coexistence of TERT promoter and BRAF mutationsin cutaneous melanoma is associated with more clinicopathological features ofaggressiveness. Virchow's Arch 467:177-184.
  4. Miao Y et al (2015) TERT promoter mutation is absent in oral mucosal melanoma. Oral Oncol 51:e65-66.

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Last updated on: 23.11.2022