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RET Rearrangements (ret + rearrangement)
Selected AbstractsRET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma componentsHISTOPATHOLOGY, Issue 3 2010Kunio Mochizuki Mochizuki K, Kondo T, Nakazawa T, Iwashina M, Kawasaki T, Nakamura N, Yamane T, Murata S-i, Ito K, Kameyama K, Kobayashi M & Katoh R (2010) Histopathology,57, 444,450 RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components Aims:, To elucidate the genetic background of anaplastic transformation, RET rearrangements and BRAF mutation were studied in composite undifferentiated carcinomas (UCs) of the thyroid, which are UCs having papillary carcinoma (PC) components. Methods and results:, Reverse transcription,polymerase chain reaction (RT,PCR) was performed for RET rearrangements and PCR for BRAF mutation in UC and PC components that were microdissected separately from seven composite UCs. Forty-two thyroid cancers with single component histology (14 UCs and 28 PCs) were also studied in the same manner. RET/PTC1 was undetectable in both components from all seven composite UCs, and RET/PTC3 was identified in both components of one composite UC. BRAF mutation was identified in both components from three composite UCs and only in the PC components from two composite UCs. In contrast, in thyroid carcinomas with single component histology, RET/PTC1 was detected in 11% of PCs and in none of the UCs, and RET/PTC3 was not found in any of the tumours studied. BRAF mutation was identified in 82% of PCs and in 21% of UCs. Conclusions:, The high frequency of BRAF mutation and the absence of RET rearrangements in UC components from composite UCs supports the hypothesis that UCs may actually represent progressive malignant degeneration of a BRAF -mutated, well-differentiated thyroid carcinoma. [source] Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinomaBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2000T. J. Musholt Background The genetic background of papillary thyroid carcinoma (PTC) has been elucidated by the identification of somatic translocations of the tyrosine kinases RET and NTRK1. Expression of RET/PTC chimeras has been demonstrated in 10,25 per cent of sporadic PTCs while rearrangements of NTRK1 were detected less frequently. Based upon the limited data available, some investigators have hypothesized that RET/PTC activation is preferentially associated with slow growing tumours of low malignancy in elderly patients, while other studies support the contrary. Methods Tumour tissues from 115 patients with sporadic PTC were harvested at operation and snap frozen. Following RNA extraction, expression analysis of the RET proto-oncogene as well as the NTRK1 gene was performed by multiplex reverse transcriptase,polymerase chain reaction. Samples with suspected rearrangements of the genes were further analysed for expression of the hybrid messenger RNAs RET/PTC1 to RET/PTC4, and for known NTRK1 chimeras. Clinical data of all patients were documented in an extensive database of thyroid carcinomas maintained by this research group. Results Twenty-one (18 per cent) of 115 tumour samples revealed somatic rearrangements of RET while translocations of the NTRK1 gene were demonstrated in 2 per cent of all samples analysed to date. The mean age of all patients was 52 (range 14,86, median 54) years and that of patients positive for RET rearrangements was 49 (range 14,82, median 49) years. Nine of 21 RET -rearranged tumours showed aggressive behaviour with locally invasive tumour growth and infiltration of adjacent structures such as muscles, vessels and trachea. Tumour samples without detectable RET translocations were associated with organ-exceeding tumour growth in only 20 per cent of cases. Conclusion These data represent one of the most comprehensive studies on gene translocations and their clinical significance in PTC. In accordance with international publications, an incidence of 2 per cent of NTRK1 rearrangements and 18 per cent of RET translocations is reported, which is in contrast to other national reports of low rearrangement rates. Somatic translocations were associated with tumours demonstrating aggressive behaviour in almost half of patients with PTC in all age groups, indicating a prognostic role of oncogenic RET/PTC activation. © 2000 British Journal of Surgery Society Ltd [source] The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studiesCLINICAL ENDOCRINOLOGY, Issue 5 2010Marina Muzza Summary Objective, The recent concept that oncogenes responsible for thyroid neoplastic transformation are able to elicit an inflammatory protumourigenic microenvironment raises interest in further studies on papillary thyroid cancer (PTC) associated with thyroid autoimmunity. Patients, The clinical and molecular features, and the expression of inflammation-related genes, were investigated in a large series of PTCs with and without associated thyroiditis (groups A, n = 128 and B, n = 215). Results, The two groups did not show significant differences in clinical and prognostic features, whereas they harboured a significantly different genetic background (P = 0·001), with RET/PTC1 being more represented in PTCs associated with autoimmunity, and BRAFV600E in patients with PTC alone. A RET/PTC rearrangement was also found in 41% of non-neoplastic thyroiditis tissues, contralateral to tumours harbouring either RET/PTC or BRAF mutations. The expression of genes encoding CCL20, CXCL8 and l -selectin was significantly higher in PTC specimens (either with RET/PTC, BRAFV600E or unknown genetic lesion) compared with normal thyroid samples. On the contrary, thyroiditis showed l -selectin expression levels even higher than PTCs, but CCL20 and CXCL8 levels comparable with normal tissues. Conclusions, The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer. [source] Hyalinizing trabecular tumour of the thyroid,differential expression of distinct miRNAs compared with papillary thyroid carcinomaHISTOPATHOLOGY, Issue 5 2010Sien-Yi Sheu Sheu S-Y, Vogel E, Worm K, Grabellus F, Schwertheim S & Schmid K W (2010) Histopathology56, 632,640 Hyalinizing trabecular tumour of the thyroid,differential expression of distinct miRNAs compared with papillary thyroid carcinoma Aims:, To compare the expression pattern of five microRNAs (miRNAs) (146b, -181b, -21, -221, -222) of papillary thyroid carcinoma (PTC) and hyalinizing trabecular tumour of the thyroid (HTT). Methods and results:, The expression pattern of five miRNAs known to be up-regulated in PTC was retrospectively analysed in 18 HTTs, adjacent normal thyroid tissue, 10 PTCs, 10 follicular adenomas and 10 non-toxic multinodular goitres (MNG) by reverse transcriptase-polymerase chain reaction using the TaqMan miRNA assay. Furthermore, the two common genetic alterations characteristic for PTC, the V600E mutation of the BRAF gene and RET/PTC 1 and 3 rearrangements, were determined in all HTTs. All miRNAs were significantly up-regulated in PTCs, whereas all miRNAs in HTT, normal thyroid tissue, adenomas, and MNGs were down-regulated. Calculating relative changes in gene expression, a 510-fold change of miRNA 146b between PTC and HTT could be observed followed by fold changes between 6.4 and 29 in the remaining miRNAs (P < 0.001). All HTTs lacked BRAF mutations and RET/PTC rearrangements. Conclusions:, Our findings do not support the concept that a high proportion of HTT represents a variant of PTC. It is suggested that HTTs lacking both a miRNA expression pattern characteristic for PTC and RET/PTC rearrangements are re-designated as ,hyalinizing trabecular adenomas'. [source] Lack of association between BRAF V600E mutation and mitogen-activated protein kinase activation in papillary thyroid carcinomaPATHOLOGY INTERNATIONAL, Issue 1 2007Hui Zuo The BRAF V600E mutation has been identified in a high proportion of papillary thyroid carcinoma (PTC). In cell lines and a transgenic mouse model it has been demonstrated that the mutation constitutively activates the mitogen-activated protein kinase (MAPK) pathway but in human PTC samples its effects remain unexamined. Herein the correlation of BRAF mutation and MAPK activation was examined in 42 human PTC samples. Activating mutations of the BRAF gene and all three RAS genes were detected by polymerase chain reaction-direct sequencing, and RET/PTC1 rearrangements were screened by nested reverse transcription,polymerase chain reaction. MAPK activation was assessed by immunohistochemistry and western blot analysis. Twenty-eight cases (66.7%) of BRAF V600E mutation, three cases (7.1%) of RET/PTC1 rearrangement but no cases of RAS genes mutation were identified. Activated MAPK was found in six cases (14.3%) with only two cases of mutant BRAF. In total 7.1% of PTC with BRAF mutation had activated MAPK. Furthermore, BRAF mutations were more prevalent in patients 0e;45 years, but did not correlate with aggressive clinical behaviors. Absence of association between BRAF mutation and activation of MAPK pathway in PTC suggests the presence of mechanisms that downregulate MAPK activation. [source] | ||||||||||