Recent Progress of Genome Study for Anaplastic Thyroid Cancer

Abstract

Anaplastic thyroid cancer (ATC) belongs to the most malignant and rapidly progressive human thyroid cancers and its prognosis is very poor. Also, it shows high resistance to cancer treatments, so that effective treatment for ATC has not been found to date, and virtually all patients terminate their life rapidly after diagnosis. Although targeted treatment of genetic alterations has emerged as an extremely promising approach to human cancers, such as BRAF in metastatic melanoma, it remains unclear that how commonly genomic alterations are influenced in ATC tumorigenesis. In recent years, genome wide approaches have been exploited to find genetic alterations associated with complex diseases, including cancer. Here, we reviewed the comprehensive genetic alterations in ATC and recent approaches in the context of identifying genomic alterations associated with ATC. Since surprisingly few reports have been published on the genome wide study of ATC, this review puts emphasis on the urgent needs of genomic research for the prevention and treatment of ATC.

Autophagy: A potential target for thyroid cancer therapy (Review)

“…A review of the molecular studies on thyroid cancer demonstrated that the Ras/Raf/mitogen-activated protein kinase kinase̸extracellular signal-regulated kinase (also referred to as mitogen-activated protein kinase; MAPK) and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways are key to the development and progression of thyroid cancer, which are associated with tumorigenesis, proliferation, apoptosis, angiogenesis, metastasis and metabolism (2,5,10,11). The MAPK signaling pathway involves a series of serine/threonine protein kinases that convert extracellular stimuli into a wide range of cellular responses through transmembrane protein receptors, such as epidermal growth factor receptor/vascular endothelial growth factor (VEGF)/rearranged during transfection (RET) (12,13).…”

“…Thyroid cancer includes differentiated thyroid cancer (DTC), poorly differentiated and undifferentiated thyroid cancer. Papillary thyroid cancer (PTC), accounting for 80-85% and follicular thyroid cancer (FTC), accounting for 10-25% of the cases, are the most common subtypes of DTC, with Hürthle cell thyroid cancer, originating from thyroid follicular cells, accounting for 1-2% of DTCs (2). Anaplastic thyroid cancer (ATC), accounting for ~1.7% of the cases, is a subtype of thyroid cancer that develops from DTC, which has lost its iodine uptake ability, has become highly aggressive and is associated with a poor prognosis, with a median survival of ~5 months and an 1-year survival rate of 20% (3,4).…”

Anaplastic thyroid cancer – an overview of genetic variations and treatment modalities

“…34 Limited epigenetic studies looking at microRNA and promoter methylation have also been performed on ATC tumors with some promise, but they are yet to come to the forefront as potent diagnostic markers. 28 ATCs are typified by hits to multiple signal transduction and cell cycle pathways (Table 1) such as TP53, PTEN-PI3K/ AKT, RAS/RAF/MAPK, and Wnt/β-catenin ( Figure 2A). Mutations in RAS (N-or H-) and BRAF which are also present in PTC suggest that they could be early oncogenic events, compounded by those in TP53, PI3K, and β-catenin resulting in progression to the aggressive dedifferentiated ATC phenotype.…”

“…[24][25][26] Multiple studies using arrayCGH (array comparative genomic hybridization) has shown that besides copy number changes, 8,27 chromosomal gains and losses as well as gene rearrangements involving the RET proto-oncogene are also present in ATC. 28 In an attempt to identify novel markers or therapeutic targets, immunohistochemistry as a tool has been used extensively to evaluate loss or overexpression of various signaling molecules.…”

“…Since significant progress has not been made in the identification of novel diagnostic markers specific to ATC due to the rarity of this cancer, the limited studies 28 that have identified some potential markers will hopefully make the cut to diagnostic markers in the near future. Meanwhile, current genetic testing of thyroid nodules is much more applicable to the detection of differentiated cancers, given that ATC does seem to develop on the background of PTC and FTC, genetic testing is indeed beneficial in early detection of these morphotypes of thyroid cancer.…”