Test Catalog

Test ID: TERT    
TERT Promoter Analysis, Tumor

Useful For Suggests clinical disorders or settings where the test may be helpful

Assisting in central nervous system tumor classification

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, slide review will always be performed at an additional charge.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

TERT gene encodes the catalytic subunit of telomerase, an enzyme complex that regulates telomere length. TERT promoter mutations in 2 hotspots (C228T and C250T) have been shown to increase telomerase activity and contribute to tumorigenesis by allowing cancer cells to overcome cellular senescence. Among central nervous system tumors, TERT promoter mutations have primarily been identified in adults, with highest frequencies in oligodendroglioma, primary glioblastoma, solitary fibrous tumor, and medulloblastoma. Although less frequent, TERT promoter mutations have also been observed in lower-grade infiltrating (diffuse and anaplastic) astrocytomas and ependymoma, and are rare or absent in other central nervous system tumor types. The presence of TERT promoter mutations have been associated with a less favorable prognosis in lower-grade (grade II/III) diffuse gliomas that lack IDH1/2 mutations and have intact 1p/19q ("IDH-wildtype astrocytomas"), and with a more favorable prognosis in prognosis in grade II/III IDH1/2-mutant and 1p/19q-codeleted diffuse gliomas ("IDH-mutant and 1p/19q codeleted oligodendrogliomas"). Assessment of TERT promoter mutation status in central nervous system tumors may assist in tumor classification and provide prognostically relevant information for subgroups of patients with lower-grade diffuse gliomas.

 

TERT gene mutations are also observed in a variety of non-central nervous system (CNS) tumor types. In hepatocellular neoplasms TERT promoter mutations occur frequently in hepatocellular carcinomas and are believed to be an early step in hepatocarcinogenesis. However, TERT promoter mutations are not specific to hepatocellular carcinoma and have been reported as a key alteration in the rare progression of hepatocellular adenomas to hepatocellular carcinomas. As such, identification of a TERT promoter mutation suggests a hepatocellular neoplasm with an increased risk for aggressive behavior.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretative report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test cannot differentiate between somatic and germline alterations. Additional testing may be necessary to clarify the significance of results if there is a potential hereditary risk.

 

This test is not intended for use for hematological malignancies.

 

DNA variants of uncertain significance may be identified.

 

A negative (wild-type) result does not rule out the presence of a mutation that may be present but below the limits of detection of this assay.

 

Point mutations and small insertion/deletion mutations will be detected with in the promoter region of the TERT gene only.

 

This test does not detect structural variants, genomic copy number variants, or large single or multiexon deletions or duplications in the TERT gene.

 

Rare polymorphisms may be present that could lead to false-negative or false-positive results. Test results should be interpreted in the context of clinical findings, tumor sampling, and other laboratory data. If results obtained do not match other clinical or laboratory findings, contact the laboratory for updated interpretation. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Reliable results are dependent on adequate specimen collection and processing. This test has been validated on cytology slides and formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause PCR failure.

Supportive Data

We have developed a next-generation sequencing assay to detect somatic mutations that can be used to assist in the classification and prognostication of central nervous system tumors.

 

This assay has been shown to be very reproducible, having a 100% concordance for intra- and interassay reproducibility experiments. All somatic mutations that had been previously identified by various other molecular methods were detected by this assay during accuracy studies. No pathogenic variants were detected in known mutation negative samples.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Killela PJ, Reitman ZJ, Jiao Y, et al: TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA. 2013;110(15):6021-6026

2. Brennan CW, Verhaak RG, McKenna A, et al: The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462-477

3. Koelsche C, Sahm F, Capper D, et al: Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. Acta Neuropathol. 2013 Dec;126(6):907-915

4. Eckel-Passow JE, Lachance DH, Molinaro AM, et al: Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med. 2015;372(26):2499-2508

5. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, et al: Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med. 2015;372(26):2481-2498

6. Bell RJ, Rube HT, Xavier-Magalhaes A, et al: Understanding TERT Promoter Mutations: A Common Path to Immortality. Mol Cancer Res. 2016;14(4):315-323

7. Horn S, Figl A, Rachakonda PS, et al: TERT promoter mutations in familial and sporadic melanoma. Science. 2013;339(6122):959-961

8. Huang FW, Hodis E, Xu MJ, et al: Highly recurrent TERT promoter mutations in human melanoma. Science. 2013;339(6122):957-959

9. Huang DS, Wang Z, He XJ, et al: Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation. Eur J Cancer. 2015 May;51(8):969-976

10. Pekmezci M, Rice T, Molinaro AM, et al: Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT. Acta Neuropathol 2017

11. Nault JC, Zucman-Rossi J: TERT promoter mutations in primary liver tumors. Clin Res Hepatol Gastroenterol. 2016 Feb;40(1):9-14Epub 2015 Aug 31

12. Schulze K, Imbeaud S, Letouzé E, et al: Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015 May;47(5):505-511