TERT Gene Analysis

Labeled mocroscope slides with tumor cells

Fixed Tissue: Ambient

Non-fixed Tissue: Frozen

Slides are prepared by Surgical Pathology, Cytopathology, Autopsy, or Dermatopathology

Specimens with less than 20% tumor cells. Incomplete and/or incorrect specimen identification.

TERT mutation not detected.

21 days

Next Generation Sequencing

Molecular Diagnostics Laboratory

TERT Promoter, TERT

In conjunction with clinical findings and other relevant data, this test is used to diagnose malignancy, assess prognosis, or recommend therapy. This test is not designed to detect minimal residual disease.

Tumor sample / sample with tumor cells

81345

The TERT gene encodes the catalytic subunit of telomerase, an enzyme that maintains telomere length and genomic integrity. TERT expression is low or absent in somatic cells; however, telomerase activity is upregulated in a vast majority of tumors and likely contributes to cancer cell immortality (PMID: 24657534, 9282118). Sequencing of the TERT promoter identified activating mutations in a number of cancer types including melanoma, hepatocellular carcinoma, urothelial carcinoma, medulloblastoma and glioma (PMID: 23348506, 23530248). Tumors with highly recurrent TERT promoter mutations tend to originate from tissues with lower rates of self-renewal (PMID: 23530248). TERT promoter mutations, C228T and C250T, account for the majority of the somatic TERT promoter alterations and occur 124 and 146 base pairs upstream of the ATG start codon of TERT, respectively. Both promoter mutations create binding motifs for erythroblast transformation-specific (ETS)/ T-cell factor (TCF) transcription factors and enhance telomerase activity (PMID: 23348503, 23348506, 26194807). In addition to promoter mutations, TERT, located on chromosome 5p, is amplified across many cancer types (PMID: 20164920).

Test information: The test is performed using the Illumina TruSight Oncology 500 (TSO500) assay (Illumina, San Diego), run on the Illumina NextSeq 550Dx instrument. It targets 523 genes to assess a wide range of DNA and RNA variant types, including single nucleotide variants (SNVs), insertions and deletions (INDELs), copy number variations (CNVs), RNA fusions, microsatellite instability (MSI), and tumor mutational burden (TMB). This assay is a targeted hybrid-capture next-generation sequencing (NGS) test, enabling comprehensive genomic profiling (CGP) of pan solid tumors. Sequencing data are analyzed using DRAGEN TruSight Oncology 500 Analysis Software v2.6.2 and Illumina Connected Insights (ICI) v5.4.0, utilizing somatic-only sequencing. The GRCh37 (hg19) reference genome is used to identify genetic variants.

The limit of detection (LoD) for minor alleles in SNVs/INDELs is approximately 5%. DNA copy number gain/amplification is reported for fold changes ≥2.8, corresponding to ≥5.6 estimated copies in the mixed tumor–normal specimen. This assay cannot detect homozygous deletions and cannot reliably assess DNA copy number in mixed tumor–normal specimens. The detection limit for RNA fusions is approximately 25 copies. For TMB measurement, it counts the total number of synonymous and nonsynonymous somatic coding SNV/INDEL variants. TMB-high is defined as having ≥10 mutations per megabase (mut/Mb). Microsatellite Instability (MSI) results are classified into three categories: High, when >20% of markers are unstable; Indeterminate, when 10– 19% of markers are unstable; and Stable, when <10% of markers are unstable. 

Limitations: This test does not detect variants outside the targeted genomic regions or those below the limit of detection. It does not identify deep intronic variants. The test analyzes variants in tumor tissue but cannot distinguish between somatic and germline variants. If hereditary or familial cancer is a concern, further evaluation and genetic counseling should be considered before additional testing. In some cases, variants may remain undetected due to technical limitations, such as the presence of known pseudogenes, GC-rich regions, repetitive or homologous sequences, and variants located in regions overlapping with amplicon primers.

Clinical Disclaimer: Results from this test must always be interpreted alongside clinical findings and other relevant data. They should not be used in isolation to diagnose malignancy, assess prognosis, or recommend therapy. Furthermore, this test is not designed to detect minimal residual disease.

This test was developed, and its performance characteristics determined by UTMB Molecular Diagnostics Laboratory. It has not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA does not require this test to go through premarket FDA review. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing. The result is not intended to be used as the sole means for clinical diagnosis or patient management decisions.

References:

1) Illumina TSO500 assay package insert and assay data sheet (TruSight Oncology 500 and TruSight Oncology 500 High-Throughput).

2) NCCN, ASCO and other relevant clinical practice guidelines.