Table 2.

Altered tumor-suppressor genes involved in thyroid cancer pathogenesis.

Tumor Suppressor Gene	Normal Function of Protein Product	Type of Alterations	Affected Thyroid Tumors	Mutation Frequency
TP53	Cell-cycle regulation	Point mutations, negative regulation by MDM family members, and ubiquitination. Dual function: oncogene and TSG	ATC (50–80%), PTC	40% in PTC, 60% in ATC
PTEN	Cell division regulation	Point mutations, deletion, promoter hypermethylation, LOH, ubiquitination, and post-translational modifications	FTC, DTC, ATC, and PTC	65–85%
APC	The regulation of cell division, adhesion, and migration	Nonsense and missense mutations, frameshift mutations, polymorphisms, and epigenetic regulation	ATC, MTC, PTC, FTC, and CMVPTC	87% in FAP-associated PTC
RASAL1	The stimulation of the GTPase activity of RAS	Missense and nonsense mutations, promoter hypermethylation	PTC, ATC, FTC, and MTC	17% in ATCs, 5% in FTCs, and 3% in PTCs
TP63	The regulation of cell proliferation and differentiation, the transactivating effect, or dominant negative activity on p53 target genes	Downregulation, dual function: oncogene and TSG	PTC and FTC
TP73	Involved in cellular responses to stress and development	Downregulation and upregulation, dual function: oncogene and TSG	Follicular adenoma, FTC, and PTC
RB	The control of DNA replication and cell division during cell damage	Mutations, deletions, downregulation, enhanced phosphorylation, and the loss of expression	MTC, PTC	1.8% in MTC
PRKAR1A	Promoting cell growth and division	Downregulation, LOH	FTC, ATC	LOH of the PRKAR1A(CA)n locus in 37.5% of cases
CHEK2	Cell-cycle control	Mutations, polymorphisms	PTC, FTC, and DTC	15.2%

PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; ATC, anaplastic thyroid cancer; MTC, medullary thyroid carcinoma; DTC, differentiated thyroid carcinoma; CMVPTC, cribriform-morular variant of papillary thyroid carcinoma; and LOH, loss of heterozygosity.