Abstract
The purpose of this paper is to correlate the molecular phenotype of papillary thyroid carcinoma (PTC) to their biological pathology. We hybridized 26 PTC on microarrays and showed that nearly 44% of the transcriptome was regulated in these tumors. We then combined our data set with two published PTC microarray studies to produce a platform- and study-independent list of PTC-associated genes. We further confirmed the mRNA regulation of 15 genes from this list by quantitative reverse transcription–PCR. Analysis of this list with statistical tools led to several conclusions: (1) there is a change in cell population with an increased expression of genes involved in the immune response, reflecting lymphocyte infiltration in the tumor compared to the normal tissue. (2) The c-jun N-terminal kinase pathway is activated by overexpression of its components. (3) The activation of ERKK1/2 by genetic alterations is supplemented by activation of the epidermal growth factor but not of the insulin-like growth factor signaling pathway. (4) There is a downregulation of immediate early genes. (5) We observed an overexpression of many proteases in accordance with tumor remodeling, and suggested a probable role of S100 proteins and annexin A2 in this process. (6) Numerous overexpressed genes favor the hypothesis of a collective migration mode of tumor cells.
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Acknowledgements
We thank Chantal Degraef for her excellent technical assistance. We acknowledge the confirmation of diagnosis provided by the International Pathology Panel of the Chernobyl Tissue Bank: Dr Alexandr Abrosimov, Professor Masahiro Ito, Professor Virginia LiVolsi, Professor Juan Rosai and Professor Sir Dillwyn Williams. This work was supported by Ministère de la Politique Scientifique (PAI), Action Concertée de la Communauté Française, Fonds National de la Recherche Scientifique, Fonds de la Recherche Scientifique Médicale, Télévie and Fondation Van Buuren. Laurent Delys is supported by Télévie, Vincent Detours by European Union's Marie Curie grant MEIF-CT-2003-501459, Frédérick Libert by the Fonds National de la Recherche Scientifique. The works of all authors were not cited in this paper due to a limitation of space. We apologize for it. Microarray data accession number:GSE3950 (GEO database, NCBI).
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).
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Delys, L., Detours, V., Franc, B. et al. Gene expression and the biological phenotype of papillary thyroid carcinomas. Oncogene 26, 7894–7903 (2007). https://doi.org/10.1038/sj.onc.1210588
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DOI: https://doi.org/10.1038/sj.onc.1210588
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