First Report of Pre-operative Detection of Two TERT Promoter Mutations Within a Papillary Thyroid Carcinoma

Introduction

Telomeres are condensed DNA-protein structures on the ends of chromosomes. Over the life of a cell, telomeres shorten with cell division, leading to DNA damage and decreased cellular proliferation. Telomerase activation, which can occur with telomerase reverse transcriptase promoter (TERT) mutations, is a phenomenon cancer cells use to maintain telomere length and induce cell immortality (figure 1).¹

TERT promoter mutations are associated with aggressive thyroid cancer and are most prevalent in anaplastic and poorly differentiated thyroid cancer.

Pre-operative thyroid nodule molecular testing can detect TERT, denoting a high risk of malignancy and possible aggressive clinical features such as extrathyroidal extension and regional (if not distant) metastases.

There are two described hot spot point mutations: the more common C228T and the less common C250T variant. Canonically, these mutations are mutually exclusive and drive monoallelic TERT expression. In this report, we describe a case of both the C228T and C250T variants being detected in the same thyroid cancer.