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      UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas

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          Abstract

          The hybridisation of an Affymetrix HG_U95Av2 oligonucleotide array with RNAs extracted from six human thyroid carcinoma cell lines and a normal human thyroid primary cell culture led us to the identification of the UbcH10 gene that was upregulated by 150-fold in all of the carcinoma cell lines in comparison to the primary culture cells of human normal thyroid origin. Immunohistochemical studies performed on paraffin-embedded tissue sections showed abundant UbcH10 levels in thyroid anaplastic carcinoma samples, whereas no detectable UbcH10 expression was observed in normal thyroid tissues, in adenomas and goiters. Papillary and follicular carcinomas were only weakly positive. These results were further confirmed by RT–PCR and Western blot analyses. The block of UbcH10 protein synthesis induced by RNA interference significantly reduced the growth rate of thyroid carcinoma cell lines. Taken together, these results would indicate that UbcH10 overexpression is involved in thyroid cell proliferation, and may represent a marker of thyroid anaplastic carcinomas.

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          Most cited references33

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          PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas.

          We recently detected a novel activated oncogene by transfection analysis on NIH 3T3 cells in five out of 20 primary human thyroid papillary carcinomas and in the available lymph node metastases. We designated this transforming gene PTC (for papillary thyroid carcinoma). Here we describe the molecular cloning and sequencing of the gene. The new oncogene resulted from the rearrangement of an unknown amino-terminal sequence to the tyrosine kinase domain of the ret proto-oncogene. This gene rearrangement was detected in all of the transfectants and in all of the original tumor DNAs, but not in normal DNA of the same patients, thus indicating that this genetic lesion occurred in vivo and is specific to somatic tumors. Moreover, the transcript coded for by the fused gene was detected in an additional PTC-positive human papillary carcinoma for which mRNA was available.
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            The WHO histological classification of thyroid tumors: a commentary on the second edition.

            This article introduces the revised WHO classification of thyroid tumors, giving an account of the major changes made and the reasons behind the changes, as well as listing the actual classification now recommended. It is intended to draw general attention to the revision, the full version of which will be published separately.
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              PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected].

              Chromosomal translocations that encode fusion oncoproteins have been observed consistently in leukemias/lymphomas and sarcomas but not in carcinomas, the most common human cancers. Here, we report that t(2;3)(q13;p25), a translocation identified in a subset of human thyroid follicular carcinomas, results in fusion of the DNA binding domains of the thyroid transcription factor PAX8 to domains A to F of the peroxisome proliferator-activated receptor (PPAR) gamma1. PAX8-PPARgamma1 mRNA and protein were detected in 5 of 8 thyroid follicular carcinomas but not in 20 follicular adenomas, 10 papillary carcinomas, or 10 multinodular hyperplasias. PAX8-PPARgamma1 inhibited thiazolidinedione-induced transactivation by PPARgamma1 in a dominant negative manner. The experiments demonstrate an oncogenic role for PPARgamma and suggest that PAX8-PPARgamma1 may be useful in the diagnosis and treatment of thyroid carcinoma.
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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                02 August 2005
                16 August 2005
                22 August 2005
                : 93
                : 4
                : 464-471
                Affiliations
                [1 ]Dipartimento di Biologia e Patologia Cellulare e Molecolare c/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II', via Pansini, 5, 80131 Naples, Italy
                [2 ]Dipartimento di Anatomia Patologica e Citopatologia, Facoltà di Medicina e Chirurgia di Napoli, Università di Napoli ‘Federico II', via Pansini, 5, 80131 Naples, Italy
                [3 ]Department of Clinical Biochemistry, Aarhus University Hospital, Skejby DK 8200 Aarhus N, Denmark
                [4 ]Service d'Anatomo-Pathologie, Centre Hospitalier Lyon Sud, Pierre Bénite, France
                [5 ]NOGEC (Naples Oncogenomic Center)-CEINGE, Biotecnologie Avanzate, via Comunale Margherita, 80131 Naples, Italy
                Author notes
                [* ]Author for correspondence: afusco@ 123456napoli.com
                Article
                6602721
                10.1038/sj.bjc.6602721
                2361574
                16106252
                29734464-b7fd-440f-b7e3-629fe4a48d61
                Copyright 2005, Cancer Research UK
                History
                : 02 March 2005
                : 16 June 2005
                : 22 June 2005
                Categories
                Molecular Diagnostics

                Oncology & Radiotherapy
                immunohistochemistry,thyroid,carcinomas,ubch10
                Oncology & Radiotherapy
                immunohistochemistry, thyroid, carcinomas, ubch10

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