Korean J Endocr Surg.  2010 Jun;10(2):79-87. 10.16956/kjes.2010.10.2.79.

Thyroid Tumorigenesis

• Park JW

• KMID: 2375721
• DOI: http://doi.org/10.16956/kjes.2010.10.2.79

Abstract

Thyroid tumors display an intriguing biological diversity from benign follicular adenomas to lethal anaplastic carcinomas. Thyroid tumorigenesis is becoming better understood. Benign follicular adenomas are frequently associated with mutation of the thyrotrophin receptor, G alpha s or RAS. Although confirmatory studies are necessary, the present knowledge concerning the similarity in gene expression profiling between follicular adenomas and follicular carcinomas supports the progression of adenoma to carcinoma sequence. Four major genetic aberrations in follicular cellderived thyroid carcinomas such as papillary, follicular, and Hurthle cell carcinomas include mutations of BRAF or RAS, and chromosomal rearrangement of RET/papillary thyroid tumor or PAX8/peroxisome proliferator-activated receptor gamma. Differentiated thyroid carcinomas of follicular cell origin dedifferentate to poorly differentiated or anaplastic thyroid carcinomas through mutation of p53 and CTNNB1. Familial nonmedullary thyroid carcinomas are heterogenous in genetic profiling, but some genes have been investigated as candidates for causative genetic aberration. Ret mutations can cause medullary thyroid carcinomas. A genotype- phenotype relationship helps to decide prophylactic thyroidectomiesin family members of hereditary medullary carcinomas such as MENIIa or MENIIb. Primary thyroid lymphomasare closely related with Hashimoto's thyroiditis. Recent novel and promising findings include additional abnormalities in the regulation of microRNA expression, polymorphisms associated with thyroid cancer susceptibility and epigenetic changes. A newly proposed fetal cell carcinogenesis hypothesis explains more about thyroid tumorigenesis than classical multi-step carcinogenesis model, but is not yet firmly supported by evidence. Future studies need to uncover new molecular mechanisms in thyroid tumorigenesis and to provide novel therapeutic targets for thyroid carcinomas.

Keyword

Tumorigenesis; Mutation; Chromosomal rearrangement; microRNA; Epigenetic changes

MeSH Terms

Adenoma
Biodiversity
Carcinogenesis*
Carcinoma
Carcinoma, Medullary
Epigenomics
Gene Expression Profiling
Humans
MicroRNAs
Phenotype
Thyroid Carcinoma, Anaplastic
Thyroid Gland*
Thyroid Neoplasms
Thyroiditis
Thyrotropin
MicroRNAs
Thyrotropin

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