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Oncogenes and tumor suppressor genes in thyroid nodules and nonmedullary thyroid cancer

Carl D Malchoff, MD
Section Editor
Douglas S Ross, MD
Deputy Editor
Jean E Mulder, MD


A thyroid tumor develops when the growth of a single thyroid epithelial cell escapes from the normal mechanisms regulating cell division and gains a selective growth advantage. Continued growth leads in time to a clinically evident tumor mass. Unregulated cell division can result from mutations in both oncogenes and tumor suppressor genes.

Although thyroid epithelial tumors arise from the same cell type, they have diverse clinical characteristics. Most produce less thyroid hormone than normal thyroid tissue, but a few produce more. Most are adenomas, but some are slow-growing cancers, and a few are highly aggressive cancers.

An understanding of the mutations of the proto-oncogenes and tumor suppressor genes that occur in these tumors may explain the diverse clinical characteristics of thyroid tumors, provide diagnostic information, and direct therapy. Some insights have already emerged; some abnormalities in tumor genes are consistently associated with specific clinical and pathologic findings. These genetic abnormalities usually represent somatic (acquired) mutations, as opposed to inherited (germline) mutations. Most thyroid tumors are sporadic and not familial. This is different from the multiple endocrine neoplasia (MEN) syndromes in which the primary tumorigenic gene mutations are inherited. (See "Classification and genetics of multiple endocrine neoplasia type 2".)

This topic review will discuss the tumorigenic gene changes found in thyroid epithelial (nonmedullary) tumors. A summary of these changes is found in the table (table 1). Medullary thyroid cancer is included in this table for comparison but is discussed elsewhere, as are the characteristics and treatment of the specific tumors. (See "Medullary thyroid cancer: Clinical manifestations, diagnosis, and staging" and "Medullary thyroid cancer: Treatment and prognosis" and "Papillary thyroid cancer" and "Follicular thyroid cancer (including Hürthle cell cancer)" and "Anaplastic thyroid cancer".)


Autonomously functioning thyroid adenomas (or nodules) are benign tumors that produce thyroid hormone. Clinically, they present as a single nodule that is hyperfunctioning ("hot") on thyroid radionuclide scan, sometimes causing hyperthyroidism. (See "Diagnostic approach to and treatment of thyroid nodules".)


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Literature review current through: Jul 2017. | This topic last updated: Aug 09, 2017.
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