Test Id : TERTT

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

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

This assay requires at least 20% tumor nuclei.

-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue 216 mm(2)

-Minimum amount of tumor area: tissue 36 mm(2)

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

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

-For specimen preparation guidance, see Tissue Requirement for Solid Tumor Next-Generation Sequencing. In this document, the sizes are given as 4mm x 4mm x 10 slides as preferred: approximate/equivalent to 144 mm(2) and the minimum as 3mm x 1mm x 10 slides: approximate/equivalent to 36 mm(2).

Preferred:

Specimen Type: Tissue block

Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block with acceptable amount of tumor tissue.

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 of the tumor tissue.

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

Additional Information: Unused unstained slides will not be returned.

Specimen Type: Cytology slides (direct smears or ThinPrep)

Slides: 1 to 3 Slides

Collection Instructions: Submit 1 to 3 slides stained and cover slipped with a preferred total of 5000 nucleated cells, or a minimum of at least 3000 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.

• Tissue Requirements for Solid Tumor Next-Generation Sequencing

If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.

See Specimen Required

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

This test uses targeted next-generation sequencing to test for the presence of somatic mutations in the promoter region of the TERT gene including c.-124 (C228T) and c.-146 (C250T).

This test is performed to evaluate for somatic mutations within solid tumor samples. It does not assess for germline alterations within region tested.

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

TERT gene encodes the catalytic subunit of telomerase, an enzyme complex that regulates telomere length. Mutations in the TERT promoter primarily involve the mutational hotspot positions c.-124 (also known as C228) and c.-146 (also known as C250) and 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.

An interpretive report will be provided.

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

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.

DNA variants of uncertain significance may be identified.

A negative result does not rule out the presence of a variant that may be present but below the limits of detection of this assay. The analytical sensitivity of this assay for sequence reportable alterations is 5% mutant allele frequency with a minimum coverage of 500X in a sample with 20% or more tumor content.

Point mutations and small insertion/deletion mutations will be detected in the TERT promoter region only. This test does not detect large single or multi-exon deletions or duplications or genomic copy number variants in TERT promoter region.

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, tumor sampling, histopathological, and other laboratory data. If results obtained do not match other clinical or laboratory findings, contact the laboratory for discussion. Misinterpretation of results may occur if the information provided is inaccurate and/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 polymerase chain reaction failure.

Performance Characteristics

The limit of detection for calling a somatic variant (single nucleotide variants [SNV] and deletions/insertions [delins, formerly indels]) is 5% variant allele frequency and having at least 500x deduplicated coverage.

Verification studies demonstrated concordance between this test and the reference method for detection of SNV and delins is 99.7% (699/701) and 96.6% (226/234) of variants, respectively. Concordance for the detection of delins was 98.9% (186/188) in variants 1 to 10 base pair (bp) in size, 95.8% (23/24) in variants 11 to 50 bp in size, and 88.9% (8/9) in variants 51 to 200 bp in size.

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

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 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, 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 May;47(5):505-511

• Tissue Requirements for Solid Tumor Next-Generation Sequencing

Next-generation sequencing is performed to test for the presence of the hotspot c.-124 (C228T) and c.-146 (C250T) mutations in the promoter region of the TERT gene.(Unpublished Mayo method)

A pathology review and macro dissection to enrich for tumor cells are performed prior to slide scraping

Monday through Friday

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• 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.

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

88381–Microdissection, manual

81345

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