. 2021 Feb 4;32(1):63–76. doi: 10.1007/s12022-021-09665-2

Table 1.

Common driver mutations and somatic genetic alterations in poorly differentiated and anaplastic thyroid carcinomas compared with differentiated thyroid carcinoma^a

Differentiated thyroid carcinoma	Poorly differentiated thyroid carcinoma^b	Anaplastic thyroid carcinoma
RAS (30–50%)^d PAX8/PPPARG (10–30%) TERT (10–35%)^f PIK3CA (0–10%) PTEN (0–10%) Can be genetically unstable and aneuploid, median number of mutations: up to 5ⁱ RAS-like TCGA molecular profile^j	BRAF V600E (40–80%) RET/PTC (5–20%)^e TERT (5–15%)^f RAS (0–10%)^d NTRK rearrangement (0–10%)^g Genetically stable, median number of mutations: 1 ± 1ⁱ BRAF V600E-like TCGA molecular profile^j	RAS (20–50%)^d TERT (20–50%)^f TP53 (10–35%) BRAF V600E (1–10%)ⁱ PTEN (5–20%) PIK3CA (0–15%) EIF1AX (5–15%)^h ALK rearrangement (0–10) Genetically unstable, aneuploid, median number of mutations: 2 ± 3ⁱ Typically have RAS-like TCGA molecular profile^j	TP53 (40–80%) TERT (30–75%)^f RAS (10–50%)^d BRAF V600E (10–50%) PIK3CA (5–25%) PTEN (10–15%) EIF1AX (5–15%)^h ALK rearrangement (0–10) Genetically unstable, highly aneuploid, median number of mutations: 6 ± 5ⁱ May have RAS-like or BRAF V600E-like TCGA molecular profile^j

Differentiated thyroid carcinoma

Poorly differentiated thyroid carcinoma^b

Anaplastic thyroid carcinoma

Follicular carcinoma^c

Papillary carcinoma (conventional types)

RAS (30–50%)^d

PAX8/PPPARG (10–30%)

TERT (10–35%)^f

PIK3CA (0–10%)

PTEN (0–10%)

Can be genetically unstable and aneuploid, median number of mutations: up to 5ⁱ

RAS-like TCGA molecular profile^j

BRAF V600E (40–80%)

RET/PTC (5–20%)^e

TERT (5–15%)^f

RAS (0–10%)^d

NTRK rearrangement (0–10%)^g

Genetically stable, median number of mutations: 1 ± 1ⁱ

BRAF V600E-like TCGA molecular profile^j

RAS (20–50%)^d

TERT (20–50%)^f

TP53 (10–35%)

BRAF V600E (1–10%)ⁱ

PTEN (5–20%)

PIK3CA (0–15%)

EIF1AX (5–15%)^h

ALK rearrangement (0–10)

Genetically unstable, aneuploid, median number of mutations: 2 ± 3ⁱ

Typically have RAS-like TCGA molecular profile^j

TP53 (40–80%)

TERT (30–75%)^f

RAS (10–50%)^d

BRAF V600E (10–50%)

PIK3CA (5–25%)

PTEN (10–15%)

EIF1AX (5–15%)^h

ALK rearrangement (0–10)

Genetically unstable, highly aneuploid, median number of mutations: 6 ± 5ⁱ

May have RAS-like or BRAF V600E-like TCGA molecular profile^j

^aMain molecular alterations, in parentheses the estimated mutation prevalence range

^bPoorly differentiated thyroid carcinoma according to Turin criteria [9]

^cEncapsulated follicular variant papillary thyroid carcinoma, with invasion or without invasion (NIFTP) have molecular alterations like that of follicular thyroid carcinoma

^dMutations in N-, H, K-RAS; N-RAS is the gene most frequently mutated

^eThe prevalence of RET/PTC is higher in children and much higher in radiation-associated papillary thyroid carcinomas

^fTERT promoter mutations: C228T [c.-124G > A] and C250T [c.-146G > A]

^gThe prevalence of NTRK rearrangements is variably reported between 0 and 5% for NTRK1 and NTRK3 in most series from non-radiation associated papillary carcinoma in adult patients; the prevalence is higher in children and young patients, and in radiation-associated papillary carcinoma

^hEIF1AX mutations occur in RAS mutated tumors

ⁱThe mutation burden per tumor is estimated from: Cancer Genome Atlas Research Network [5] Landa I et al. [15] Pozdeyev N et al. [20]

^jThe Cancer Genome Atlas (TCGA), Integrated Genomic Characterization of Papillary Thyroid Carcinoma [5]