Oncogenes and predicting clinical outcomes in thyroid cancer

Coinciding with World Cancer Day, this month’s issue of our journal Endocrine-Related Cancer includes an exciting new review of cutting edge research on a putative new oncogene TERT, and its role in affecting clinical outcomes in thyroid cancer. Journal editor Charis Eng is here to tell us why this is such a significant piece of work.

 
Over the last 10 years, thyroid cancer has been the fastest rising incident cancer in women and second fastest in men, without clear aetiology.  In the January 2016 issue of Endocrine-Related Cancer, Liu and Xing from Johns Hopkins University School of Medicine provided an authoritative review article on “TERT promoter mutations and their role in predicting clinical outcome in thyroid cancer”.

Up until recently, BRAF and RAS somatic mutations were utilized to predict outcome in thyroid cancer.  Two years ago, Prof Xing was the first to show that TERT promoter mutations were associated with the most aggressive thyroid cancers.  Now, the authors bring us an erudite and comprehensive review on this new and cutting edge field.

The oncogenic role of TERT promoter mutations involve creation of consensus binding sites for ETS transcriptional factors.   The mutations occur with an increasing prevalence from low- to high-grade thyroid tumours, namely, on average, 0%, 11.3%, 17.1%, 43.2%, and 40.1% in benign thyroid tumours, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer, and anaplastic thyroid cancer, respectively (Figure 1). They are strongly associated with aggressive clinicopathological outcomes, including aggressive pathological features, tumour recurrence, and patient mortality.  Importantly, TERT promoter mutations are also associated with BRAF and RAS mutations, and their coexistence has a robust synergistic effect on the poor clinicopathological outcomes of thyroid cancer.

This review by Liu and Xing conclude that the mutated TERT gene is a prominent new oncogene that plays an important role in thyroid tumorigenesis and represents a novel diagnostic and prognostic molecular marker and therapeutic target in this cancer.

 

 

Fig 1

Figure 1. Prevalence of TERT promoter mutations increases with the grade of the thyroid tumour and is associated with more aggressive clinicopathological outcomes.

 

To find out more on the latest endocrine cancer research across all our journals, visit our new website Hormone-Related Cancer.

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