TERT Promoter Mutation Assay

Paraffin-embedded (FFPE) tissue block or slides

Paraffin-embedded tissue (FFPE) block

Two unstained slides at 5µm and one matching H&E slide or three unstained slides at 5µm. Tumor surface area ≥ 4mm2 tumor area and ≥ 50% tumor content are preferred.

FFPE tissue block and slide container

Telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of telomerase, which maintains telomere length. The two most commonly impacted sites for TERT promoter mutations are located 124 and 146 base pairs upstream from the translational start site, and generate C to T transitions (-124C>T and -146C>T). These two hotspots comprise 100% of the mutations reported in glioma, and >98% of the mutations detected in the TERT promoter across all tumor types. TERT promoter mutations create novel binding sites for ETS/TCF family of transcription factors such as GA Binding Protein Transcription Factor Subunit Alpha (GABPA) and increase TERT expression ~2-6 fold. The -146C>T mutation also creates a binding site for non-canonical NF-KB subunit p52 and ETS1/2.

Somatic mutations in the TERT promoter have been shown to cause TERT upregulation in a wide range of solid cancers, including central nervous system tumors, melanoma, urothelial carcinoma, poorly differentiated and anaplastic thyroid carcinomas, cutaneous basal cell and squamous cell carcinomas, and hepatocellular carcinoma. In glioma and glioblastoma multiforme (GBM), the frequency of TERT promoter mutations varies by WHO grade. Assessment of TERT promoter mutation status, in addition to IDH mutations and 1p/19q co-deletion, could help refine the WHO 2016 classification of gliomas in diagnosis and allow for precise clinical management of the patients.

In vitro studies indicate that this assay has a sensitivity to detect approximately 5% mutated TERT in a background of non-mutant DNA. Mutations present at a level below the detection sensitivity or outside the analyzed region of the TERT genes will not be detected by this assay.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Genomic DNA was isolated from the provided tumor specimen. The promoter region of TERT gene was subjected to SNaPshot multiplex PCR and primer extension for mutation detection. This assay is able to detect 5% mutation in a background of wild-type DNA. This test can detect the following hotspot mutations in the TERT promoter: -146C>T (C250T) and -124C>T (C228T).