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# 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.

Updated Nov 12, 2026

## Key points

- Papillary: BRAF V600E (most) or fusions of RET (RET/PTC), NTRK1/3, ALK or BRAF.
- Follicular, NIFTP and encapsulated follicular variant (RAS-like): RAS mutations, PAX8-PPARG, PTEN or PIK3CA.
- Dedifferentiation: TP53 and TERT promoter mutations, mostly in poorly differentiated and anaplastic carcinomas.
- Medullary: RET activating point mutations (germline in MEN2, somatic in many sporadic tumours).
- Radiation in childhood (Chernobyl, therapeutic) raises papillary carcinoma, often with RET or NTRK fusions.
- Many drivers are drug targets (BRAF, RET, NTRK inhibitors).

## 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](https://durgical.com/en/conditions/thyroid-cancer/) | BRAF V600E; RET, NTRK, ALK fusions | MAP kinase | Fusions commoner after radiation and in children |
| [Follicular adenoma and carcinoma](https://durgical.com/en/conditions/follicular-oncocytic-and-anaplastic-thyroid-carcinoma/) | RAS; PAX8-PPARG | MAP kinase and PI3K-AKT | Same drivers in benign and malignant |
| [NIFTP and encapsulated follicular variant](https://durgical.com/en/conditions/thyroid-cancer/) | RAS | MAP kinase | Behaves like follicular neoplasm |
| [Oncocytic carcinoma](https://durgical.com/en/conditions/follicular-oncocytic-and-anaplastic-thyroid-carcinoma/) | Mitochondrial DNA mutations, chromosomal losses | Energy metabolism | Distinct from follicular |
| [Poorly differentiated and anaplastic](https://durgical.com/en/conditions/follicular-oncocytic-and-anaplastic-thyroid-carcinoma/) | Earlier driver plus TP53, TERT promoter | Loss of genome guardians | Arise from well-differentiated tumours |
| [Medullary carcinoma](https://durgical.com/en/conditions/medullary-thyroid-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.

## Memory aid

Papillary wears BRAF or a fusion; follicular wears RAS; both turn into anaplastic when TP53 and TERT walk in.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/thyroid-cancer-genetics-and-radiation/)

[More Pathology questions →](https://durgical.com/en/practice/?f=pathology)

## Elsewhere in DurgiPedia

- [Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know](https://durgical.com/en/general-pathology/oncogenes-ras-myc-her2-bcr-abl-and-the-table-to-know/)
- [Radiation and cancer: ultraviolet and ionizing](https://durgical.com/en/general-pathology/radiation-and-cancer-ultraviolet-and-ionizing/)
- [Multistep carcinogenesis: the adenoma–carcinoma sequence](https://durgical.com/en/general-pathology/multistep-carcinogenesis-the-adenoma-carcinoma-sequence/)

## Connections

## Related 6

- [Papillary thyroid carcinoma](https://durgical.com/en/general-pathology/papillary-thyroid-carcinoma/)
- [Follicular thyroid carcinoma and NIFTP](https://durgical.com/en/general-pathology/follicular-thyroid-carcinoma-and-niftp/)
- [Poorly differentiated and anaplastic thyroid carcinoma](https://durgical.com/en/general-pathology/poorly-differentiated-and-anaplastic-thyroid-carcinoma/)
- [Medullary thyroid carcinoma](https://durgical.com/en/general-pathology/medullary-thyroid-carcinoma/)
- [Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know](https://durgical.com/en/general-pathology/oncogenes-ras-myc-her2-bcr-abl-and-the-table-to-know/)
- [Radiation and cancer: ultraviolet and ionizing](https://durgical.com/en/general-pathology/radiation-and-cancer-ultraviolet-and-ionizing/)

## Related conditions 3

- [Thyroid cancer (papillary)](https://durgical.com/en/conditions/thyroid-cancer/)
- [Follicular, oncocytic (Hürthle cell) and anaplastic thyroid carcinoma](https://durgical.com/en/conditions/follicular-oncocytic-and-anaplastic-thyroid-carcinoma/)
- [Medullary thyroid carcinoma](https://durgical.com/en/conditions/medullary-thyroid-carcinoma/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq) (National Cancer Institute, 2025); [Papillary Thyroid Carcinoma](https://www.ncbi.nlm.nih.gov/books/NBK536943/) (StatPearls (NCBI Bookshelf), 2025).

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Source: https://durgical.com/en/general-pathology/thyroid-cancer-genetics-and-radiation/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/thyroid-cancer-genetics-and-radiation/