ECE2009 Poster Presentations Endocrine tumours and neoplasia (53 abstracts)
Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue
Sabrina Corbetta 1 , Valentina Vaira 2 , Vito Guarnieri 3 , Alfredo Scillitani 4 , Cristina Eller-Vainicher 5 , Leonardo Vicentini 6 , Jacopo Chiodini 5 , Michele Bisceglia 7 , Paolo Beck-Peccoz 5 , Silvano Bosari 2 & Anna Spada 5
1Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, University of Milan, IRCCS Policlinico S. Donato, S. Donato M.se, Italy; 2Pathology Unit, Department of Medicine, Surgery and Dentistry, University of Milan, A.O.S. Paolo, and IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy; 3Unit of Medical Genetics, IRCCS Hospital Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy; 4Unit of Endocrinology, IRCCS Hospital Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy; 5Endocrine Unit, Department of Medical Sciences, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Regina Elena, Mangiagalli, Milan, Italy; 6Endocrine Surgery, IRCCS Fondazione Ospedale Maggiore Policlinico, Regina Elena, Mangiagalli, Milan, Italy; 7Unit of Pathology, IRCCS Hospital Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy.
Parathyroid carcinoma is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism-jaw tumor syndrome and in a consistent set of sporadic parathyroid carcinomas, parathyroid carcinogenesis remains obscure. MicroRNAs (miRNAs) are a new class of small, non-coding RNAs implicated in embryonic development and cancer. A deregulated miRNA can induce the aberrant expression of several target genes. The aim of the present study was to identify differentially expressed miRNAs in parathyroid cancers compared to normal parathyroid tissues. We performed a TaqMan low-density array-based profiling of 4 parathyroid cancers harboring an inactivating mutation in HRPT2 gene and negative for parafibromin immunostaining. Their miRNA profiling was compared with that of two normal parathyroid biopsies. Out of 362 human miRNAs assayed, 279 (77%) were expressed above background levels in all samples. Unsupervised hierarchical clustering correctly classified the normal specimens from the tumors. Fourteen and 3 miRNAs were significantly down- and over-expressed in parathyroid cancers, respectively. Of these, SAM analysis identified 2 miRNAs (296 and 139) and 2 miRNAs (503 and 222) significantly down- and over-expressed, respectively, with a null false discovery rate. In particular, miRNA-296 was able to discriminate with the highest accuracy between parathyroid cancers and normal glands (P=0.0012). To further investigate the expression of miRNA-296, we analyzed its expression profile in 13 parathyroid sporadic adenomas, four atypical adenomas and two metastasis. miRNA-296 expression levels were definitely low in parathyroid cancers and metastasis as well as in atypical adenomas, while in sporadic adenomas they were reduced but not significantly different from normal samples. These results suggest a potential role of miRNA-296 as an oncosuppressor gene and indicate this miRNA as an explorative tumor marker useful for clinical diagnosis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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