Decrease in thyroid adenoma associated (THADA) expression is a marker of dedifferentiation of thyroid tissue

Lars Kloth,Rolf Nimzyk,Jörn Bullerdiek,Xin Fu,Salah A Mohamed,Käte Burchardt,Norbert Drieschner,Werner Wosniok,Gazanfer Belge,Volkhard Rippe,Siegfried Loeschke

doi:10.1186/1472-6890-11-13

Lars Kloth, Rolf Nimzyk + Show 9 more

Open Access

https://doi.org/10.1186/1472-6890-11-13

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Abstract

BackgroundThyroid adenoma associated (THADA) has been identified as the target gene affected by chromosome 2p21 translocations in thyroid adenomas, but the role of THADA in the thyroid is still elusive. The aim of this study was to quantify THADA gene expression in normal tissues and in thyroid hyper- and neoplasias, using real-time PCR.MethodsFor the analysis THADA and 18S rRNA gene expression assays were performed on 34 normal tissue samples, including thyroid, salivary gland, heart, endometrium, myometrium, lung, blood, and adipose tissue as well as on 85 thyroid hyper- and neoplasias, including three adenomas with a 2p21 translocation. In addition, NIS (sodium-iodide symporter) gene expression was measured on 34 of the pathological thyroid samples.ResultsResults illustrated that THADA expression in normal thyroid tissue was significantly higher (p < 0.0001, exact Wilcoxon test) than in the other tissues. Significant differences were also found between non-malignant pathological thyroid samples (goiters and adenomas) and malignant tumors (p < 0.001, Wilcoxon test, t approximation), anaplastic carcinomas (ATCs) and all other samples and also between ATCs and all other malignant tumors (p < 0.05, Wilcoxon test, t approximation). Furthermore, in thyroid tumors THADA mRNA expression was found to be inversely correlated with HMGA2 mRNA. HMGA2 expression was recently identified as a marker revealing malignant transformation of thyroid follicular tumors. A correlation between THADA and NIS has also been found in thyroid normal tissue and malignant tumors.ConclusionsThe results suggest THADA being a marker of dedifferentiation of thyroid tissue.

Highlights

Thyroid adenoma associated (THADA) has been identified as the target gene affected by chromosome 2p21 translocations in thyroid adenomas, but the role of THADA in the thyroid is still elusive
For the formalin-fixed paraffin-embedded (FFPE) tissues of thyroid tumors, histopathologic diagnoses were performed according to the World Health Organization Classification of Tumours [21]
THADA expression in normal tissues Thirty-four snap-frozen samples from eight different tissues were tested for the level of THADA expression

Summary

Introduction

Thyroid adenoma associated (THADA) has been identified as the target gene affected by chromosome 2p21 translocations in thyroid adenomas, but the role of THADA in the thyroid is still elusive. The target gene has been identified and referred to as thyroid adenoma associated (THADA) [3]. The THADA protein has three isoforms corresponding to the three different transcript variants with 1953 [GenBank: NP_071348], 1879, and 1832 amino acids, respectively. In adenomas with 2p21 translocations Rippe et al found different types of fusion variants of THADA [3]. THADA was truncated after exon 28 and ectopic sequences fused to it were not correlated to any known gene. It has been speculated that the truncation rather than the fusion to ectopic coding sequences is the critical event for the development of the tumor [3]

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