A Review of Driver Genetic Alterations in Thyroid Cancers

Fatemeh Khatami

doi:10.30699/ijp.13.2.125

Abstract

Thyroid cancer is a frequent endocrine-related malignancy with continuously increasing incidence, and recently the development in understanding its molecular pathogenesis is mainly through the explanation of the original role of several key signaling pathways and related molecular distributors. Central to these mechanisms are the genetic and epigenetic alterations in these pathways such as mutation and DNA rearrangements. However, it does not mean that all the somatic abnormalities in a cancer genome are involved in cancer development and just driver mutations are concerned in tumor initiation. By way of illustrations, MAPK pathway motivated by BRAF V600E and RAS and RET / PTC rearrangements are suggesting driver genetic alterations in follicular derived thyroid cancers considered in the current review.

Highlights

Thyroid cancer is the most common endocrine related cancer that its incidence has continuously increased in the last three decades all over the world [1,2,3,4,5]
The classic treatment for thyroid cancer is thyroidectomy and adjuvant radioiodine ablation that most patients can be cured, but still surgically inoperative recurrence, refractoriness to radioiodine in differentiated thyroid cancer (DTC), poorly differentiated thyroid carcinoma and ATC are unsolved
Driver mutations and gene fusions are identified in most of thyroid cancers suggesting that two main cell signaling pathways are MAPK and PI3K-AKT involved in the development of thyroid tumors [17,21]

Summary

Introduction

Thyroid cancer is the most common endocrine related cancer that its incidence has continuously increased in the last three decades all over the world [1,2,3,4,5]. There are numerous somatic point mutations and chromosomal rearrangements have been recognized in of different steps follicular cell-derived thyroid cancer (Figure 1) [15,16] whose are mainly be- longing to the MAPK signaling pathway and RET/ PTC rearrangements [17]. Driver mutations and gene fusions are identified in most of thyroid cancers suggesting that two main cell signaling pathways are MAPK and PI3K-AKT involved in the development of thyroid tumors [17,21]. In the thyroid gland of transgenic mouse studies with conditional physiological expression of a KRAS had no transformation, but simultaneous KRAS mutant expression and PTEN deletion induced a rapid occurrence of aggressive FTC [42,43,44] Another main driver genetic alteration in thyroid cancer is the rearranged during transfusion (RET) proto-oncogene. The preferential occurrences of these mutations in PDTC and ATC, which are the most aggressive thyroid cancers, indicate to the fact that they may have a role in the progression and aggressiveness of thyroid cancer

Conclusions

4-41 PMID:19930726