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Two-Step Differential Expression Analysis Reveals a New Set of Genes Involved in Thyroid Oncocytic Tumors

Institut National de la Santé et de la Recherche Médicale, E0018, Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire (C.J., O.B., D.P.-M., F.S., P.R., V.R., Y.M., P.R.), F-49033 Angers, France; Laboratoire d’Anatomie Pathologique, Hôpital Ambroise Paré (B.F.), F-92104 Boulogne, France; and Laboratoire d’Anatomie Pathologique, Centre Hospitalier Régional Universitaire (S.G.), F-37044 Tours, France

Address all correspondence and requests for reprints to: Dr. Caroline Jacques, Institut National de la Santé et de la Recherche Médicale, E0018, Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire d’Angers, 4 rue Larrey, F-49033 Angers, France. E-mail: address: caroline.jacques{at}med.univ-angers.fr.

Thyroid oncocytic adenomas are a class of tumors characterized by the presence of abundant mitochondria. We performed a differential display RT-PCR analysis on two oncocytic adenomas and their paired controls. We then carried out a microarray analysis using the 460 selected, differentially expressed clones on four other oncocytomas and their paired controls. Thirty genes, 12 encoded by mitochondrial DNA and 18 nuclear-encoded, were overexpressed by a factor of at least 2 in the tumors compared with the controls. Seven of the 18 nuclear-encoded genes are involved in protein metabolism: DKFZP434I116, B3GTL, SNX19, RP42, SENP1, UBE2D3, and the CTSB gene, which is known to be particularly deregulated in most thyroid tumors. Other genes are implicated in signal transduction (ITGAV) or tumorigenesis (AF1q). Immunohistochemistry allowed us to confirm overexpression of the ITGAV and CTSB genes at the protein level and showed a marked relocation of the CTSB protein. We confirmed the overexpression of the AF1q oncogene in 56% of 18 oncocytic tumors by quantitative RT-PCR analysis, which attested to the heterogeneity of these tumors. Our results show an increased expression of genes involved in protein metabolism in oncocytoma, the significance of which requires investigation.

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