Identifying NTRK and RET Alterations in Differentiated Thyroid Cancer


Lova Sun, MD, discusses genetic alterations in thyroid cancer, including RET and NTRK alterations, and how these can affect treatment options.

Genetic variations can be found in different types of thyroid cancer. The most common kind, differentiated thyroid cancer, has alterations in genes like BRAF (around 50% of cases), RET (10%-20%), and NTRK (2%-4%). Other genes like RAS are also mutated in some differentiated thyroid cancers. Notably, medullary thyroid cancer has distinct RET mutations compared to differentiated types. Finally, the aggressive anaplastic thyroid cancer can also have BRAF mutations. The wide variety of genetic changes highlights the importance of advanced DNA sequencing techniques to identify specific mutations for targeted treatment of thyroid cancer.

Here, Lova Sun MD, MCSE, assistant professor of medicine at the Hospital of the University of Pennsylvania, discusses the various genetic alterations across thyroid cancer and its subtypes.


0:05 | When we think of thyroid cancer, we break it up into different histologic types. Most commonly, we're talking about differentiated thyroid cancer as well as anaplastic and medullary thyroid cancer as buckets. The most common alteration we see is BRAF, which is present in about half of those cases. About 10 to 20% of differentiated thyroid cancers harbor RET, which is in distinction to mutations in RET that we see in medullary thyroid cancer, so important to keep those distinctions in mind.

0:41 | And NTRK fusions are found, uncommonly, in about about 2 to 4% of differentiated thyroid cancers. In terms of other types of alterations, mutations in RAS,, including NRAS, can be found in papillary thyroid cancers as well as other types of differentiated thyroid cancer like follicular and Hurthle cell carcinoma, and then finally anaplastic thyroid cancer can also harbor BRAF and rarely other mutations. A lot of heterogeneity, as you can see, in the different types of alterations that we see in thyroid cancer, which really highlights the importance of using next-generation sequencing to identify these actionable alterations

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