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Identification of Differential Transcriptional Patterns in Primary and Secondary Hyperparathyroidism

Sadowski, Samira Mercedes ; Pusztaszeri, Marc ; Brulhart-Meynet, Marie-Claude ; Petrenko, Volodymyr ; De Vito, Claudio ; Sobel, Jonathan ; Delucinge-Vivier, Céline ; Kebebew, Electron ; Regazzi, Romano ; Philippe, Jacques ; Triponez, Frédéric ; Dibner, Charna

In: The Journal of Clinical Endocrinology & Metabolism, 2018, vol. 103, no. 6, p. 2189-2198

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    Title
    • Identification of Differential Transcriptional Patterns in Primary and Secondary Hyperparathyroidism
    Author
    • Sadowski, Samira Mercedes. Department of Thoracic and Endocrine Surgery, University Hospitals of Geneva and Faculty of Medicine, University of Geneva, Geneva, Switzerland
    • Pusztaszeri, Marc. Division of Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland
    • Brulhart-Meynet, Marie-Claude. Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospitals of Geneva, Geneva, Switzerland
    • Petrenko, Volodymyr. Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospitals of Geneva, Geneva, Switzerland
    • De Vito, Claudio. Division of Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland
    • Sobel, Jonathan. Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland
    • Delucinge-Vivier, Céline. iGE3 Genomics Platform, University of Geneva, Geneva, Switzerland
    • Kebebew, Electron. Department of Surgery, Stanford University, California
    • Regazzi, Romano. Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland
    • Philippe, Jacques. Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospitals of Geneva, Geneva, Switzerland
    • Triponez, Frédéric. Department of Thoracic and Endocrine Surgery, University Hospitals of Geneva and Faculty of Medicine, University of Geneva, Geneva, Switzerland
    • Dibner, Charna. Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospitals of Geneva, Geneva, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • The Journal of Clinical Endocrinology & Metabolism, 2018, vol. 103, no. 6, p. 2189-2198. Endocrine Society
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:331330
    Summary
    Abstract Context Hyperparathyroidism is associated with hypercalcemia and the excess of parathyroid hormone secretion; however, the alterations in molecular pattern of functional genes during parathyroid tumorigenesis have not been unraveled. We aimed at establishing transcriptional patterns of normal and pathological parathyroid glands (PGs) in sporadic primary (HPT1) and secondary hyperparathyroidism (HPT2). Objective To evaluate dynamic alterations in molecular patterns as a function of the type of PG pathology, a comparative transcript analysis was conducted in subgroups of healthy samples, sporadic HPT1 adenoma and hyperplasia, and HPT2. Design Normal, adenomatous, HPT1, and HPT2 hyperplastic PG formalin-fixed paraffin-embedded samples were subjected to NanoString analysis. In silico microRNA (miRNA) analyses and messenger RNA-miRNA network in PG pathologies were conducted. Individual messenger RNA and miRNA levels were assessed in snap-frozen PG samples. Results The expression levels of c-MET, MYC, TIMP1, and clock genes NFIL3 and PER1 were significantly altered in HPT1 adenoma compared with normal PG tissue when assessed by NanoString and quantitative reverse transcription polymerase chain reaction. RET was affected in HPT1 hyperplasia, whereas CaSR and VDR transcripts were downregulated in HPT2 hyperplastic PG tissue. CDH1, c-MET, MYC, and CaSR were altered in adenoma compared with hyperplasia. Correlation analyses suggest that c-MET, MYC, and NFIL3 exhibit collective expression level changes associated with HPT1 adenoma development. miRNAs, predicted in silico to target these genes, did not exhibit a clear tendency upon experimental validation. Conclusions The presented gene expression analysis provides a differential molecular characterization of PG adenoma and hyperplasia pathologies, advancing our understanding of their etiology.