Within every thyroid nodule lies a genetic story. Molecular testing helps decode that story by analyzing mutations that can help identify whether the nodule is benign or malignant, and can potentially reduce unnecessary surgeries.
Molecular diagnostic testing platforms, like ThyGeNEXT®+ThyraMIR®v2, provide analyses that include the identification of mutations that help to rule in or diagnose thyroid cancer, predict the likelihood of aggressive biological features, and identify potential candidates for FDA-approved targeted therapies.1-6
But what exactly are mutations, and why do they matter?
What are Mutations?7
Mutations are changes in a cell’s DNA sequence that can alter its structure and function, impacting cellular growth and behavior. Mutations may be harmful, beneficial, or have no effect at all. While most mutations help control essential processes—such as cell growth, division, DNA repair, and cell death—problematic mutations can8:
- Cause uncontrolled growth and spread
- Turn off DNA repair genes
- Cause resistance to cell death
Certain mutations may lead to diseases, such as cancer, or can simply increase the risk of disease.7,8
Why Understanding Mutations Through Molecular Testing is Important9-11
Molecular testing of indeterminate thyroid nodules can identify strong driver mutations—such as ALK, RET, TERT Promoter, and BRAF V600E—which can be useful in the diagnosis and prognosis of thyroid carcinoma. The presence of these mutations can also help inform surgical decision-making.
The ThyGeNEXT panel includes the most common mutations associated with thyroid cancer.12
| Papillary Thyroid Carcinoma | Follicular Subtype of Papillary Thyroid Carcinoma | Follicular Carcinoma | Medullary Carcinoma | Follicular Adenoma |
|---|---|---|---|---|
| BRAF (V600E) | RAS | RAS | RET | RAS |
| RET/PTC | PAX8/PPARG | PAX8/PPARG | RAS | PAX8/PPARG |
| RAS | BRAF (K601E) | PIK3CA | PTEN | |
| NTRK | RET/PTC | PTEN | TSHR | |
| TERT | TERT | GNAS |
For example, clinical research has shown that TERT Promoter and ALK mutations can reliably help to predict aggressive features of thyroid cancer, including large tumor size, higher recurrence rates post-treatment, and increased likelihood of cancer spreading beyond the thyroid.3-6
Understanding the presence of specific mutations identified by molecular testing provides insight that other diagnostic approaches might miss. By analyzing specific mutations, physicians can provide more accurate risk stratification and reduce surgeries on benign nodules.
The ThyGeNEXT+ThyraMIRv2 testing platform utilizes both mutational and microRNA markers, with microRNAs able to help rule in malignancy even in the absence of identified mutations, helping provide a complete picture to improve risk assessment of indeterminate thyroid nodules.9,13
FAQs
What mutations are important when risk-stratifying indeterminate thyroid nodules?
In cases where cytology results are inconclusive, identifying the presence of specific mutations can provide deep insights to help when risk-stratifying indeterminate thyroid nodules. Mutations such as ALK, RET, TERT Promoter, and BRAF V600E are considered strong driver mutations and are well-documented as being associated with thyroid carcinoma. Understanding their presence (or absence) can be useful in diagnosis and prognosis, as well as being helpful in surgical decision-making.9-11
Which mutations identified by ThyGeNEXT are aligned to FDA-approved targeted therapies for thyroid carcinoma?
The ThyGeNEXT panel identifies worrisome and coexisting mutations, including those that provide therapeutic insight.1,2,9 When present, test results identify the mutations that are aligned to FDA-approved targeted therapies for thyroid carcinoma. These mutational markers are1,2:
- ALK
- BRAF
- RET
- NTRK
Identifying these mutational markers can help aid patient management decisions and identify potential targeted therapy options for FDA-approved targeted therapies.1,2,9
How does ThyGeNEXT+ThyraMIRv2 help improve risk stratification of indeterminate thyroid nodules?
ThyGeNEXT+ThyraMIRv2 is a unique combination testing platform that utilizes an assessment of the most common mutations associated with all types of thyroid carcinoma and microRNA signatures that provide deep insight into the epigenetic regulation of cancer signaling pathways. The assessment of microRNAs with ThyraMIRv2 enables the testing platform to help rule in malignancy, even in the absence of identified mutations by ThyGeNEXT.9,13 This dual assessment helps provide a complete picture, improving the risk assessment of indeterminate thyroid nodules from a mutational analysis alone.9,13
Patient management decisions are based on the independent medical judgment of the physician and molecular test results should be taken into consideration in conjunction with all relevant imaging, clinical findings, patient and family history, as well as patient preference.
References: 1. Drugs Approved for Solid Tumors Anywhere in the Body. National Cancer Institute. Accessed May 20, 2022. www.cancer.gov/about-cancer/treatment/drugs/solid-tumors. 2. Drugs Approved for Thyroid Cancer. National Cancer Institute. Accessed May 20, 2022. www.cancer.gov/about-cancer/treatment/drugs/thyroid. 3. Liu X, et al. Endocr Relat Cancer. 2013;20(4):603-610. doi:10.1530/ERC-13-0210. 4. Melo M, et al. J Clin Endocrinol Metab. 2014;99(5):E754-E765. doi:10.1210/jc.2013-3734. 5. Yang X, et al. J Nucl Med. 2017;58(2):258-265. doi:10.2967/jnumed.116.180240. 6. Xing M. Nat Rev Cancer. 2013;13(3):184-199. doi:10.1038/nrc3431. 7. The genetics of cancer. National Cancer Institute. Accessed September 26, 2023. https://www.cancer.gov/about-cancer/causes-prevention/genetics/. 8. https://www.cancer.org/cancer/understanding-cancer/genes-and-cancer/gene-changes.html 9. Finkelstein SD, et al. Thyroid. 2022;32(11):1362-1371.10. Panebianco F, et al. Endocr Relat Cancer. 2019;26(11):803-814. doi:10.1530/ERC-19-0325. 11. Pekova B, et al. Cancers (Basel). 2021;13(8):1932. doi:10.3390/cancers13081932. 12. Hsiao SJ and Nikiforov YE. Molecular Advances in the Diagnosis and Treatment of Thyroid Cancer. Ento Key. June 1, 2020. Accessed October 23, 2023. https://entokey.com/10- molecular-advances-in-the-diagnosis-and-treatment-of-thyroid-cancer. 13. Lupo MA, et al. Diagn Cytopathol. 2020;48(12):1254-1264.
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