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N Ameur, Gustave Roussy, Villejuif, France
L Lacroix, Gustave Roussy, Villejuif, 94805, France
S Roucan, Gustave Roussy, Villejuif, 94805, France
R Veronique, Functional Genomic Unit, Institut Gustave-Roussy, Villejuif, France
S Broutin, Gustave Roussy, Villejuif, France
M Talbot, Gustave Roussy, Villejuif, France
C Dupuy, Gustave Roussy, Villejuif, France
B Caillou, Gustave Roussy, Villejuif, France
M Schlumberger, Gustave Roussy, Villejuif, France
J Bidart, Gustave Roussy, Villejuif, France

Correspondence: Nabahet Ameur, Email: ameurnabahet{at}yahoo.fr

Abstract

RET oncogene mutations are found in familial medullary thyroid carcinomas (MTC) and in one third of sporadic cases. Oncogenic mechanisms involved in non-RET mutated sporadic MTC remain unclear. To study alterations associated with the development of both inherited and sporadic MTC pangenomic DNA microarrays were used to analyze the transcriptome of 13 MTCs (4 familial and 9 sporadic). By using an ANOVA test, a list of 173 gene sequences with at least a two-fold change expression, was obtained. A subset of differentially expressed genes was controlled by real time quantitative PCR and immunohistochemistry on a larger collection of MTCs. The expression pattern of those genes allowed to distinguish 2 groups of sporadic tumors. The first group displays an expression profile similar to that expressed by inherited RET634 tumors. The second presents an expression profile close to that displayed by inherited RET918 tumors and includes tumors from patients with distant metastases. It is characterized by the overexpression of genes involved in proliferation and invasion (PTN, ESM1, and CEACAM6) or matrix remodelling (COL1A1, COL1A2, FAP). Interestingly, RET918 tumors showed overexpression of the PTN gene, encoding pleiotrophin, a protein associated to metastasis. Using a MTC cell line, silencing of RET induced inhibition of PTN gene expression. Overall, our results suggest that familial MTC and sporadic MTC could activate similar oncogenic pathways.