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EZH2 and ZFX oncogenes in malignant behaviour of parathyroid neoplasms

  • Endocrine Genetics/Epigenetics
  • Published:
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Abstract

Several studies reported somatic mutations of many genes (MEN1, CTNNB1, CDKIs and others) in parathyroid adenoma, although with different prevalence. Recently, activating mutations of the EZH2 and ZFX oncogenes were identified in benign parathyroid adenoma by whole exome sequencing. The same mutations had been found in blood and ovary malignant tumours. On one hand, this result raised the hypothesis that these oncogenes may play a role in the onset of parathyroid tumour, but it would also suggest they may be involved in malignant, rather benign, parathyroid neoplasm. Our aim was to verify the occurrence of selected mutations of the EZH2 and ZFX genes in an Italian cohort of 23 sporadic parathyroid carcinomas, 12 atypical and 45 typical adenomas. DNA was extracted from paraffin-embedded tissues, PCR amplified and directly sequenced. No mutations were detected in the coding sequence and boundaries of both genes in any of the samples. Two polymorphisms of the EZH2 gene were identified with different prevalence: the rs2072407 variant was present in the 30 % of the samples, in keeping with the overall frequency in larger populations, while the rs78589034 variant, located close to the 5′ end of the exon 16, was detected in only one proband with familial isolated hyperparathyroidism; we investigated the possible outcome on the splicing process. EZH2 and ZFX genes do not seem to have an impact on the onset of most parathyroid tumours, both benign and malignant, though further studies on larger cohorts of different ethnicity are needed.

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Acknowledgments

The authors gratefully acknowledge the families participating in this study and Andreina Guarnieri for helpful revision of the English language. This research was supported by the Ricerca Corrente and Finalizzata-GR-2011-02351489 funding granted by the Italian Ministry of Health (to VG) and by the “5 × 1000” voluntary contributions. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Medical Genetics, Poliambulatorio Giovanni Paolo II, IRCCS Casa Sollievo della Sofferenza Hospital, 71013, San Giovanni Rotondo, FG, Italy

    E. Sanpaolo, M. Miroballo, F. Baorda, L. Cinque & Vito Guarnieri

  2. Endocrinology Unit, Department of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy

    S. Corbetta

  3. Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy

    T. Balsamo, F. P. Fabrizio & L. A. Muscarella

  4. Pathology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy

    P. Graziano

  5. Endocrinology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy

    A. Scillitani

  6. Laboratory of Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy

    C. Verdelli

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  1. E. Sanpaolo
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Sanpaolo, E., Miroballo, M., Corbetta, S. et al. EZH2 and ZFX oncogenes in malignant behaviour of parathyroid neoplasms. Endocrine 54, 55–59 (2016). https://doi.org/10.1007/s12020-016-0892-y

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  • DOI: https://doi.org/10.1007/s12020-016-0892-y

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