Two-step differential expression analysis reveals a new set of genes involved in thyroid oncocytic tumors.
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.
Jacques
Caroline
C
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. caroline.jacques@med.univ-angers.fr
Baris
Olivier
O
Prunier-Mirebeau
Delphine
D
Savagner
Frédérique
F
Rodien
Patrice
P
Rohmer
Vincent
V
Franc
Brigitte
B
Guyetant
Serge
S
Malthiery
Yves
Y
Reynier
Pascal
P
D033742:Adenine Nucleotide Translocator 2 / Q000235:genetics; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007473:Ion Channels; D026901:Membrane Transport Proteins / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D000071246:Uncoupling Protein 2
D033742:Adenine Nucleotide Translocator 2; D004272:DNA, Mitochondrial; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D000071246:Uncoupling Protein 2