Quantitative analysis of thyroid adenoma associated (THADA) and high-mobility group AT-hook 2 (HMGA2) in dedifferentiated and extra-embryonic human tissues

Analysis of the genomic structure of THADA revealed a size of 365 kbp and 38 exons in the full-length form. In case of a truncation often found in thyroid adenomas, the breakpoints are located in intron 28, thereby translocating the 3'-end of the gene. Own research elucidated that its protein is located in the cytoplasm, independent of the existence of the carboxy terminus. THADA turned out to be a marker of dedifferentiation of thyroid tissue. In the thyroid THADA might have a particular role, since its expression turned out to be significantly higher in this organ than in several other tissues. Also, only in the thyroid a negative correlation with HMGA2 could be detected. HMGA2 is a marker for the dedifferentiation of thyroid tissue, thereby verifying the results obtained in the analysis of THADA expression. HMGA2 is known to play an important role in early development. This could be confirmed for fetal placenta samples. High qRT-PCR values were detected in samples from the first trimester, whereas a baseline expression could be observed up until birth. While HMGA2 is mostly downregulated in adult tissues, reexpression can be found in several tumors, especially in malignant neoplasias. This is also the case for testicular germ cell tumors. A subgroup-specific expression could be distinctively determined. It could also be shown, that use of qRT-PCR and immunohistochemistry on HMGA2 might serve as a marker in clinical application

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

<p>Abstract</p> <p>Background</p> <p><it>Thyroid adenoma associated (THADA) </it>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 <it>THADA </it>gene expression in normal tissues and in thyroid hyper- and neoplasias, using real-time PCR.</p> <p>Methods</p> <p>For the analysis <it>THADA </it>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, <it>NIS </it>(<it>sodium-iodide symporter</it>) gene expression was measured on 34 of the pathological thyroid samples.</p> <p>Results</p> <p>Results illustrated that <it>THADA </it>expression in normal thyroid tissue was significantly higher (<it>p </it>< 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 (<it>p </it>< 0.001, Wilcoxon test, t approximation), anaplastic carcinomas (ATCs) and all other samples and also between ATCs and all other malignant tumors (<it>p </it>< 0.05, Wilcoxon test, t approximation). Furthermore, in thyroid tumors <it>THADA </it>mRNA expression was found to be inversely correlated with <it>HMGA2 </it>mRNA. <it>HMGA2 </it>expression was recently identified as a marker revealing malignant transformation of thyroid follicular tumors. A correlation between <it>THADA </it>and <it>NIS </it>has also been found in thyroid normal tissue and malignant tumors.</p> <p>Conclusions</p> <p>The results suggest <it>THADA </it>being a marker of dedifferentiation of thyroid tissue.</p

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass

Quantitative Analyse von thyroid adenoma associated (THADA) und high-mobility group AT-hook 2 (HMGA2) in dedifferenzierten und extra-embryonalen Geweben

Analysis of the genomic structure of THADA revealed a size of 365 kbp and 38 exons in the full-length form. In case of a truncation often found in thyroid adenomas, the breakpoints are located in intron 28, thereby translocating the 3'-end of the gene. Own research elucidated that its protein is located in the cytoplasm, independent of the existence of the carboxy terminus. THADA turned out to be a marker of dedifferentiation of thyroid tissue. In the thyroid THADA might have a particular role, since its expression turned out to be significantly higher in this organ than in several other tissues. Also, only in the thyroid a negative correlation with HMGA2 could be detected. HMGA2 is a marker for the dedifferentiation of thyroid tissue, thereby verifying the results obtained in the analysis of THADA expression. HMGA2 is known to play an important role in early development. This could be confirmed for fetal placenta samples. High qRT-PCR values were detected in samples from the first trimester, whereas a baseline expression could be observed up until birth. While HMGA2 is mostly downregulated in adult tissues, reexpression can be found in several tumors, especially in malignant neoplasias. This is also the case for testicular germ cell tumors. A subgroup-specific expression could be distinctively determined. It could also be shown, that use of qRT-PCR and immunohistochemistry on HMGA2 might serve as a marker in clinical application

Meeting report ESC forum on drug eluting stents, European Heart House, Nice, 27-28 September 2007

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