Signaling pathways in follicular cell-derived thyroid carcinomas (Review)

Romitti,Mírian; Ceolin,Lucieli; Siqueira,Débora Rodrigues; Ferreira,Carla Vaz; Wajner,Simone Magagnin; Maia,Ana Luiza

doi:10.3892/ijo.2012.1681

Signaling pathways in follicular cell-derived thyroid carcinomas (Review)

Authors:
- Mírian Romitti
- Lucieli Ceolin
- Débora Rodrigues Siqueira
- Carla Vaz Ferreira
- Simone Magagnin Wajner
- Ana Luiza Maia
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Affiliations: Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Published online on: October 29, 2012 https://doi.org/10.3892/ijo.2012.1681
Pages: 19-28

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Abstract

Thyroid carcinoma is the most common malignant endocrine neoplasia. Differentiated thyroid carcinomas (DTCs) represent more than 90% of all thyroid carcinomas and comprise the papillary and follicular thyroid carcinoma subtypes. Anaplastic thyroid carcinomas correspond to less than 1% of all thyroid tumors and can arise de novo or by dedifferentiation of a differentiated tumor. The etiology of DTCs is not fully understood. Several genetic events have been implicated in thyroid tumorigenesis. Point mutations in the BRAF or RAS genes or rearranged in transformation (RET)/papillary thyroid carcinoma (PTC) gene rearrangements are observed in approximately 70% of papillary cancer cases. Follicular carcinomas commonly harbor RAS mutations and paired box gene 8 (PAX8)-peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Anaplastic carcinomas may have a wide set of genetic alterations, that include gene effectors in the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) and/or β-catenin signaling pathways. These distinct genetic alterations constitutively activate the MAPK, PI3K and β-catenin signaling pathways, which have been implicated in thyroid cancer development and progression. In this context, the evaluation of specific genes, as well as the knowledge of their effects on thyroid carcinogenesis may provide important information on disease presentation, prognosis and therapy, through the development of specific tyrosine kinase targets. In this review, we aimed to present an updated and comprehensive review of the recent advances in the understanding of the genetic basis of follicular cell-derived thyroid carcinomas, as well as the molecular mechanisms involved in tumor development and progression.

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