Thyroid Cancer: Molecular Genetics


Thyroid cancer is the most common malignancy of endocrine organs. The thyroid comprises two specialised cell types, follicular thyrocytes and C cells. Most thyroid cancers arise from thyroid follicular cells. These cancers include well‐differentiated papillary carcinoma and follicular carcinoma, poorly differentiated carcinoma and anaplastic carcinoma, whereas medullary carcinomas arise from the calcitonin‐producing C cells. Papillary and follicular carcinomas are the two most common types of thyroid cancer. Genetic alterations, including BRAF and RAS point mutations, and RET/PTC and PAX8/PPARγ rearrangements, and p53 inactivation underlines the molecular mechanisms resulting in thyroid cancer. These genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. The use of molecular markers is expected to improve the accuracy of diagnosis of thyroid cancers and inform the prognosis of each cancer. We review common genetic alterations in thyroid carcinomas and discuss the diagnostic and prognostic significance.

Key Concepts:

  • The thyroid cancers are subdivided into well‐differentiated papillary carcinoma and follicular carcinoma, poorly differentiated carcinoma, and anaplastic carcinoma.

  • Papillary carcinomas carry point mutations of the BRAF and RAS genes as well as RET/PTC and TRK rearrangement.

  • Follicular carcinomas carry either RAS mutations or PAX8/PPARγ rearrangement.

  • The knowledge of molecular genetics of thyroid cancer eventually getting the clinical impact, such as improvement of diagnostic accuracy, management of thyroid cancer, and surgical planning and can be a prognostic markers.

Keywords: papillary thyroid carcinoma; follicular carcinoma; medullary carcinoma; BRAF; RAS; RET/PTC; PAX8/PPARγ; TP53

Figure 1.

The main signalling pathways in thyroid carcinogenesis are the MAPK and P1 3K‐AKT pathways. Mutations and rearrangements that activate MAPK/ERK are the most common molecular events in thyroid oncogenesis. The MAPK/ERK and P13K/AKT cascades integrate multiple signals leading to cell growth.



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Web Links

v‐Ha‐ras Harvey rat sarcoma viral oncogene homolog (HRAS); Locus ID: 3265. LocusLink:

v‐Ha‐ras Harvey rat sarcoma viral oncogene homolog (HRAS); MIM number: 190020. OMIM:‐post/Omim/dispmim?190020

v‐Ki‐ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS2); Locus ID: 3845. Locus Link:

v‐Ki‐ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS2); MIM number: 190070. OMIM:‐post/Omim/dispmim?190070

Met proto‐oncogene (hepatocyte growth factor receptor) (MET); Locus ID: 4233. LocusLink:

Met proto‐oncogene (hepatocyte growth factor receptor) (MET); MIM number: 164860. OMIM:‐post/Omim/dispmim?164860

Neuroblastoma RAS viral (v‐ras) oncogene homolog (NRAS); Locus ID: 4893. LocusLink:

Neuroblastoma RAS viral (v‐ras) oncogene homolog (NRAS); MIM number: 164790. OMIM:‐post/Omim/dispmim?164790

Ret proto‐oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease) (RET); Locus ID: 5979. LocusLink:

Ret proto‐oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease) (RET); MIM number: 164761. OMIM:‐post/Omim/dispmim?164761

Tumor protein p53 (Li–Fraumeni syndrome) (TP53); Locus ID: 7157. LocusLink:

Tumor protein p53 (Li–Fraumeni syndrome) (TP53); MIM number: 191170. OMIM:‐post/Omim/dispmim?191170

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Son, Eun Ju, and Nosé, Vania(Apr 2012) Thyroid Cancer: Molecular Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006177.pub2]