Benign thyroid tumors and hyperplasias of follicular epithelial origin belong to the cytogenetically best analyzed human epithelial tumors.
Cytogenetic aberrations have been detected in approximately 20% of these lesions . Translocations of chromosomal band 2p21 are the second most frequent structural chromosomal rearrangement, representing a particular cytogenetic subgroup . The target gene has been identified and referred to as thyroid adenoma associated (THADA) .
The full length cDNA of THADA consists of 6,134 bp distributed over 38 exons [GenBank: NM_022065]. There are two splice-variants, one lacking exons 27 and 28 , and the other without exons 16 and 17. 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 . In each case, THADA was truncated after exon 28 and ectopic sequences fused to it were not correlated to any known gene. Thus, 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 .
Studies by Drieschner et al.  revealed that the mRNA, the protein size, and the genomic organization is conserved among Homo sapiens, Canis familiaris, Chlorocebus aethiops, Gallus gallus, and Mus musculus. THADA proteins from the analyzed organisms showed significant assignments to the superfamily ARM repeat (SSF48371; Hidden Markov Models Superfamily database), indicating the presence of a protein-protein-interaction-domain of that type.
The exact function of THADA still remains unclear. Hypothetically, it belongs to the death receptor-interacting proteins and is assumed to bind to death receptor DR5 (Puduvalli VK and Ridgway L, GenBank accession reference note), involving it in the TRAIL-induced apoptosis. The truncated THADA derived from the rearranged allele might compete with the gene product of the normal allele thereby disturbing normal apoptosis of follicular cells, and subsequently altering the steady state between proliferation and cellular death leading to adenomatous growth in benign thyroid tumors with 2p21 translocations . Nevertheless, there is a need for further studies elucidating the role of THADA in normal thyroid development and in tumorigenesis.
Recently, a THADA variant has also been linked to type 2 diabetes (T2D) , but this association has not been confirmed by the majority of further studies [6–20]. During a meta-analysis of three genome-wide association studies with individuals of European descent Zeggini et al. found evidence for an association of a SNP (rs7578597) in exon 24 of THADA and the susceptibility for T2D . Further indication for a correlation between THADA and T2D was presented in several other publications [11, 14, 16, 17, 19], one reported an altered expression of THADA in pancreatic islets, using data from the Diabetes Genome Anatomy Project (DGAP) database . In other investigations no correlation was detected [6–8, 10, 12, 13, 15, 18, 20], except for one publication , which reported an association between THADA SNP rs7578597 and a 2-h insulin level during an oral glucose tolerance test but no significant association between the THADA SNP and T2D risk, rendering the association disputable.
The aim of this study was to analyze THADA expression in thyroid tissue in comparison to other tissues and to thyroid hyper- and neoplasias to elucidate the possible correlation of THADA mRNA with thyroid differentiation and neoplastic growth.