Mutation Profile of Well-Differentiated Thyroid Cancer in Asians

Abstract

Recent advances in molecular diagnostics have led to significant insights into the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in thyroid cancers, the vast majority are associated with the mitogen-activated protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers are more likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Beyond these more common mutations, alterations in the telomerase reverse transcriptase (TERT) promoter have recently been associated with clinicopathologic features, disease prognosis, and tumorigenesis in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well known, the frequency of these mutations is strongly associated with geography, with clear differences reported between Asian and Western countries. Of particular interest is the prevalence of BRAF mutations, with Korean patients exhibiting the highest rate of BRAF-associated thyroid cancers in the world. Here, we review the prevalence of each of the most common mutations in Asian and Western countries, and identify the characteristics of well-differentiated thyroid cancer in Asians.

TERT Promoter Mutation Predicts Radioiodine-Refractory Character in Distant Metastatic Differentiated Thyroid Cancer

“…There have been studies showing that the prevalence of TERT mutation varies significantly among different countries, ranging from 4.1% to 25.5% for PTC (21)(22)(23)(24) and from 5.9% to 36.4% for follicular thyroid cancer (13,23). Among these data, the prevalence in China was reported to be 4.1%-11.3% for PTC (13,21,24), relatively lower than in western countries.…”

The Profile of Genetic Mutations in Papillary Thyroid Cancer Detected by Whole Exome Sequencing

“…PPAR pathway was composed by a group of nuclear receptors which played pivotal roles in cellular differentiation, development and lipid metabolism [35]. The abnormal activation of the signal way implicated with tumorigenesis of bladder cancer, esophageal cancer, follicular thyroid cancers, etc [36][37][38]. In this study, we found that PPAR signal pathway was involved in the progression of PTC.…”

Reply:

“…13 Musholt et al 14 considered that mutations of RET/PTC, RAS, and PAX8/peroxisome proliferator-activated receptor ␥ (PPAR␥) were predominantly associated with thyroid malignancy with varying frequency and had less impact on the clinical management. However, in the study of Song et al, 15 BRAF mutations were the most common ones observed in PTCs, followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers were more likely to have RAS mutations or PAX8/PPAR␥ rearrangements. 15 Therefore, more extensive research is needed in genetic testing.…”

“…However, in the study of Song et al, 15 BRAF mutations were the most common ones observed in PTCs, followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers were more likely to have RAS mutations or PAX8/PPAR␥ rearrangements. 15 Therefore, more extensive research is needed in genetic testing.…”