59. What the TERT? - A telomerase reverse transcriptase case study

Telomerase reverse transcriptase is a catalytic subunit of the telomerase protein that is involved in the maintenance of genomic stability. TERT aberrations are important biomarkers in the diagnosis, prognosis, and treatment of many human cancers. The TERT promoter has proven to be a difficult region of testing amongst a variety of currently available technologies.

TERT promoter mutation analysis was performed on brain tissue of a 62-year old male meningioma patient using MALDI-TOF (Agena Bioscience MassARRAY platform) and detected a low frequency TERT mutation. The pathologist questioned the result and sent some of the sample for additional testing to 2 different referral laboratories - one aliquot was sent for Pyrosequencing and the other for NGS - both with a higher limit of detection than MALDI-TOF. Neither methodology detected a TERT mutation. On the basis of these result the diagnosis was changed.

Certain of our TERT mutation, an aliquot of the remaining extracted DNA was sent for digital droplet PCR (ddPCR) which has the same limit of detection as our MALDI-TOF platform. A TERT mutation was confirmed.

This case highlights the challenges in TERT promoter mutation analysis as well as the significance of confirmatory testing. The importance of confirming results using platforms with an appropriate limit of detection is paramount in reducing under-reporting of low level mutations of clinical significance.