Novel association of MEN1 gene mutations with parathyroid carcinoma

Cinque,Luigia; Sparaneo,Angelo; Cetani,Filomena; Coco,Michelina; Clemente,Celeste; Chetta,Massimiliano; Balsamo,Teresa; Battista,Claudia; Sanpaolo,Eliana; Pardi,Elena; D'Agruma,Leonardo; Marcocci,Claudio; Maiello,Evaristo; Hendy,Geoffrey  N.; Cole,David  E.C.; Scillitani,Alfredo; Guarnieri,Vito

doi:10.3892/ol.2017.6162

Novel association of MEN1 gene mutations with parathyroid carcinoma

Authors:
- Luigia Cinque
- Angelo Sparaneo
- Filomena Cetani
- Michelina Coco
- Celeste Clemente
- Massimiliano Chetta
- Teresa Balsamo
- Claudia Battista
- Eliana Sanpaolo
- Elena Pardi
- Leonardo D'Agruma
- Claudio Marcocci
- Evaristo Maiello
- Geoffrey N. Hendy
- David E.C. Cole
- Alfredo Scillitani
- Vito Guarnieri
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Affiliations: Department of Medical Genetics, IRCCS Casa Sollievo della Sofferenza Hospital, I‑71013 San Giovanni Rotondo, Italy, Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza Hospital, I‑71013 San Giovanni Rotondo, Italy, Department of Clinical and Experimental Medicine, Endocrine Unit 2, University Hospital of Pisa, I‑56124 Pisa, Italy, Department of Pathology, IRCCS Casa Sollievo della Sofferenza Hospital, I‑71013 San Giovanni Rotondo, Italy, Laboratory of Molecular Medicine and Genomics, University of Salerno, I‑84081 Baronissi, Italy, Department of Endocrinology, IRCCS Casa Sollievo della Sofferenza Hospital, I‑71013 San Giovanni Rotondo, Italy, Department of Oncohematology, IRCCS Casa Sollievo della Sofferenza Hospital, I‑71013 San Giovanni Rotondo, Italy, Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, QC H4A 3J1, Canada, Departments of Laboratory Medicine and Pathobiology, Medicine and Genetics, University of Toronto, Toronto, ON M4N 3M5, Canada
Published online on: May 12, 2017 https://doi.org/10.3892/ol.2017.6162
Pages: 23-30
Copyright: © Cinque et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Inactivating mutations of the multiple endocrine neoplasia 1 (MEN1) gene cause MEN1 syndrome, characterized by primary hyperparathyroidism (pHPT), and parathyroid and gastro‑entero‑pancreatic pituitary tumors. At present, only 14 cases of malignant parathyroid tumor have been associated with the syndrome, with 6 cases carrying an inactivating mutation of the MEN1 gene. The present study presents the case of a 48‑year‑old female who presented with multigland pHPT and multiple pancreatic lesions. The patient underwent surgery several times for the excision of parathyroid hyperplasia, carcinoma and adenoma. The MEN1 gene was screened, revealing three variants (in cis) at the intron/exon 3 boundary (IVS2‑3G>C, c.497A>T and c.499G>T) detected on the DNA of the proband, not shared by her relatives. RNA sequencing revealed that the IVS2‑3C>G variant caused the skipping of the exon 3. Therefore, the present study reports on a novel rare association of MEN1 syndrome and parathyroid carcinoma. The reported splicing mutation was previously identified in subjects who always developed malignant lesions; thus, a possible genotype‑phenotype association may be considered.

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