Thyroid cancer: genetics and radiation
- Mechanism
Each kind of thyroid cancer has its own gene changes. Radiation to the neck in childhood is the clearest outside cause.
What it is
Carcinomas of follicular cell origin are driven mainly by gain-of-function changes in the MAP kinase and PI3K-AKT pathways, and the type of driver predicts the tumour type. Papillary carcinomas carry BRAF V600E or kinase fusions; follicular neoplasms carry RAS mutations or PAX8-PPARG fusions; progression to poorly differentiated and anaplastic carcinoma adds TP53 and TERT promoter mutations. Medullary carcinoma, from C cells, is driven by RET point mutations.
Step by step
- A first driver activates growth signalling (BRAF or a fusion in papillary; RAS or PAX8-PPARG in follicular).
- The cells form a well-differentiated carcinoma that still concentrates iodine and makes thyroglobulin.
- TERT promoter mutation lets the cells divide indefinitely; TP53 loss removes the damage checkpoint.
- Differentiation genes (iodide transporter, thyroglobulin) are switched off.
- Result: poorly differentiated or anaplastic carcinoma that no longer takes up radioiodine.
Drivers by thyroid tumour type
| Tumour | Main drivers | Pathway | Note |
|---|---|---|---|
| Papillary carcinoma | BRAF V600E; RET, NTRK, ALK fusions | MAP kinase | Fusions commoner after radiation and in children |
| Follicular adenoma and carcinoma | RAS; PAX8-PPARG | MAP kinase and PI3K-AKT | Same drivers in benign and malignant |
| NIFTP and encapsulated follicular variant | RAS | MAP kinase | Behaves like follicular neoplasm |
| Oncocytic carcinoma | Mitochondrial DNA mutations, chromosomal losses | Energy metabolism | Distinct from follicular |
| Poorly differentiated and anaplastic | Earlier driver plus TP53, TERT promoter | Loss of genome guardians | Arise from well-differentiated tumours |
| Medullary carcinoma | RET point mutation (or RAS) | Receptor tyrosine kinase | Germline RET in MEN2 |
Clinical notes
- BRAF V600E tumours trap less radioiodine; dedifferentiated tumours are radioiodine-refractory.
- Targeted drugs exist for BRAF-, RET- and NTRK-altered advanced thyroid cancers.
Test yourself
Think of the answer, then tap the question to see it.
Which mutation is most common in papillary thyroid carcinoma?
BRAF V600E.
Which fusion is found in some follicular thyroid neoplasms?
PAX8-PPARG.
Which mutations mark progression to anaplastic carcinoma?
TP53 and TERT promoter mutations added to the earlier driver.
Elsewhere in DurgiPedia
- Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know
- Radiation and cancer: ultraviolet and ionizing
- Multistep carcinogenesis: the adenoma–carcinoma sequence
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Thyroid Cancer Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025); Papillary Thyroid Carcinoma (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.