Test Catalog

Test Id : TERTD

TERT Promoter Mutation Analysis, Droplet Digital PCR, Tumor

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

Identifying specific mutations within the TERT promoter that assist in tumor diagnosis/classification

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test uses droplet digital PCR (ddPCR) to evaluate for the presence of the c.-124C>T (also known as C228T) and c.-146C>T (also known as C250T) somatic mutations in the promoter region of the TERT gene. TERT promoter analysis ddPCR is a highly sensitive testing platform that can detect the c.-124C>T (C228T) and c.-146C>T (C250T) hotspot mutations at low levels, which may be observed in specimens with low number or proportion (%) of tumor cells/cells of interest.

 

This test cannot differentiate between somatic and germline variant origin and is not intended to assess for germline risk.

Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.

Test Id Reporting Name Available Separately Always Performed
SLIRV Slide Review in MG No Yes

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.

Method Name
A short description of the method used to perform the test

Droplet Digital Polymerase Chain Reaction (ddPCR)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

TERT Promoter Analysis ddPCR, Tumor

Aliases
Lists additional common names for a test, as an aid in searching

Astrocytoma

Brain

Central Nervous System

C228

C250

CNS

Diffuse glioma

Glioblastoma

Glioma

Hepatocellular adenoma

Hepatocellular carcinoma

Liposarcoma

Melanoma

Meningioma

Droplet Digital PCR

Oligodendroglioma

Telomerase

TERTD

TERT promoter C228T and C250T

Thyroid carcinoma

Urothelial carcinoma

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.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

For the preferred test to assess for somatic hotspot mutations in the TERT, IDH1, and IDH2 genes, order IDTRT / IDH1, IDH2 and TERT Mutation Analysis, Next-Generation Sequencing, Tumor.

 

If this test is ordered with IDHT / IDH1 and IDH2 Mutations Analyses, Next-Generation Sequencing, Tumor, this test will be canceled and ordered as IDTRT.

Necessary Information

A pathology report (final or preliminary), at minimum containing the following information, must accompany specimen for testing to be performed:

1. Patient name

2. Block number-must be on all blocks, slides, and paperwork (can be handwritten on the paperwork)

3. Tissue collection date

4. Source of the tissue

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

This assay requires at least 5% nuclei of tumor cells/cells of interest.

-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue144 mm(2)

-These amounts are cumulative over up to 10 unstained slides and must have adequate percent nuclei of tumor cells/cells of interest.

-Tissue fixation: 10% neutral buffered formalin, not decalcified

-Cytology fixatives: Cytology smears fixed in alcohol and thin preps fixed with CytoLyt.

 

Preferred:

Specimen Type: Tissue block

Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block with acceptable percent nuclei of tumor cells/cells of interest.

 

Acceptable:

Specimen Type: Tissue slides

Slides: 1 Stained and 10 unstained

Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 10 unstained, nonbaked slides with 5-micron thick sections.

Note: The total amount of required cell nuclei can be obtained by scraping up to 10 slides from the same block.

 

Specimen Type: Cytology slide (direct smears or ThinPrep)

Slides: 1 to 3 slides

Collection Instructions: Submit 1 to 3 slides stained and coverslipped with a preferred total of 3000 nucleated cells or a minimum of at least 350 nucleated cells.

Note: Glass coverslips are preferred; plastic coverslips are acceptable but will result in longer turnaround times.

Additional Information: Cytology slides will not be returned.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Specimens that have been decalcified (all methods)
Specimens that have not been formalin-fixed, paraffin-embedded excluding cytology slides
Extracted nucleic acid (DNA/RNA)
Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
Refrigerated

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

Identifying specific mutations within the TERT promoter that assist in tumor diagnosis/classification

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test uses droplet digital PCR (ddPCR) to evaluate for the presence of the c.-124C>T (also known as C228T) and c.-146C>T (also known as C250T) somatic mutations in the promoter region of the TERT gene. TERT promoter analysis ddPCR is a highly sensitive testing platform that can detect the c.-124C>T (C228T) and c.-146C>T (C250T) hotspot mutations at low levels, which may be observed in specimens with low number or proportion (%) of tumor cells/cells of interest.

 

This test cannot differentiate between somatic and germline variant origin and is not intended to assess for germline risk.

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. Mutations in the TERT promoter, primarily involving mutational hotspot positions c.-124 (also known as C228) and c.-146 (also known as C250), increase telomerase activity allowing tumor cells to overcome cellular senescence. In central nervous system (CNS) tumors, TERT promoter mutations are a diagnostic and grading molecular biomarker in diffuse gliomas and meningioma. TERT promoter mutations are observed in other CNS tumor types and are not seen in CNS reactive non-neoplastic processes. TERT promoter mutations are also a molecular biomarker in non-CNS tumors, including hepatocellular tumors, melanoma, myxoid liposarcoma, thyroid carcinoma and urothelial carcinoma.

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 interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

The interpretation of molecular biomarker analysis includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.

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.

 

A negative (wildtype) result does not rule out the presence of a mutation that may be present but below the limits of detection of this assay. The analytical sensitivity of this assay for mutation detection is 1% mutant copies in a sample with 5% or more tumor cells/cells of interest.

 

This test detects TERT promoter mutations in 2 hotspots (C228T and C250T) only. Other alterations within the TERT promoter are not detectable by this test.

 

Rare alterations (ie, 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 or other treatment of tissues, such as decalcification, may cause droplet digital polymerase chain reaction failure.

Supportive Data

The TERT C228T and C250T droplet digital polymerase chain reaction (ddPCR) assays were shown to be reproducible, with 100% concordance for intra/inter-assay reproducibility experiments. Concordance between results by ddPCR and next-generation sequencing (NGS) for formalin-fixed paraffin- embedded (FFPE) samples was 98% (52/53), with the single discordant result (positive by ddPCR and negative for NGS) explained by the increased sensitivity of ddPCR relative to NGS technology. The analytical sensitivity of these assays was shown to be 1% fraction abundance of mutant copies at 2.5 ng DNA input (equivalent to at least 495 wild-type copies). All expected negative samples tested negative, and there was no cross reactivity between TERT C228T and C250T assays.

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

1. WHO Classification of Tumours Editorial Board: Central nervous system tumours. 5th ed. World Health Organization; 2021. WHO Classification of Tumours, Vol. 6

2. 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

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

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

Method Description
Describes how the test is performed and provides a method-specific reference

Droplet digital polymerase chain reaction method is performed to test for the presence of hotspot c.-124C>T (C228T) and c.-146C>T (C250T) mutations in the promoter region of the TERT gene.(Unpublished Mayo method)

Gene

GenBank Accession Number

Chromosome (Genome build)

TERT promoter

NM_198253

Chromosome 5 (GRCh37/hg19)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

8 to 10 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

FFPE tissue block: Unused portions of blocks will be returned 10 to 14 days after testing is complete; FFPE tissue/cytology slides: Unused slides are stored indefinitely and not returned; Digital images are obtained and stored for all slides used in testing.

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81345

88381-Microdissection, manual

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
TERTD TERT Promoter Analysis ddPCR, Tumor 95778-7
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
618698 Result Summary 50397-9
618699 Result 82939-0
618700 Interpretation 69047-9
618701 Additional Information 48767-8
618704 Specimen 31208-2
618705 Source 31208-2
618706 Tissue ID 80398-1
618702 Method 85069-3
618703 Disclaimer 62364-5
618707 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | PHP Pdf | CMS Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports