Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma
Objective. Atypical parathyroid adenoma is a rare neoplasm, showing atypical histological features intermediate between classic benign adenoma and the rarest parathyroid carcinoma, whose the clinical behaviour and outcome is not yet understood or predictable. Up to date only two cases of atypical ad...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2020/2080797 |
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| author | Luigia Cinque Flavia Pugliese Celeste Clemente Stefano Castellana Maria Pia Leone Danilo de Martino Teresa Balsamo Claudia Battista Tommaso Biagini Paolo Graziano Marco Castori Alfredo Scillitani Vito Guarnieri |
| author_facet | Luigia Cinque Flavia Pugliese Celeste Clemente Stefano Castellana Maria Pia Leone Danilo de Martino Teresa Balsamo Claudia Battista Tommaso Biagini Paolo Graziano Marco Castori Alfredo Scillitani Vito Guarnieri |
| author_sort | Luigia Cinque |
| collection | DOAJ |
| description | Objective. Atypical parathyroid adenoma is a rare neoplasm, showing atypical histological features intermediate between classic benign adenoma and the rarest parathyroid carcinoma, whose the clinical behaviour and outcome is not yet understood or predictable. Up to date only two cases of atypical adenoma were found associated to a MEN1 syndrome, and only one was proved to carry a pathogenic variant of the MEN1 gene. Design. We report the clinical, histologic, and molecular findings of a 44-year-old woman, presenting with a histologically proved atypical parathyroid adenoma with an apparent aggressive behaviour. Methods and Results. CDC73 gene was screened at germline and somatic levels with no results. Whole exome sequencing performed on DNA extracted from blood leukocytes and tumour tissue revealed a somatic MEN1 gene heterozygous variant, c.912+1G > A, of the splicing donor site of exon 6. On immunohistochemistry, downregulation of the menin protein expression in the neoplastic cells was also observed. Conclusions. We report the second case of a rare association of a somatic MEN1 gene mutation in a patient with atypical parathyroid adenoma. We suggest that MEN1 gene could be an underestimate genetic determinant of these rare histological entities, and we highlight the utility of a complete genetic screening protocol, by the use of next-generation sequencing technology in such undetermined clinical cases with no frank clinical presentation. |
| format | Article |
| id | doaj-art-54c9b5ffdac74c7f937495041bb1955a |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-54c9b5ffdac74c7f937495041bb1955a2025-02-03T06:05:18ZengWileyInternational Journal of Endocrinology1687-83371687-83452020-01-01202010.1155/2020/20807972080797Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid AdenomaLuigia Cinque0Flavia Pugliese1Celeste Clemente2Stefano Castellana3Maria Pia Leone4Danilo de Martino5Teresa Balsamo6Claudia Battista7Tommaso Biagini8Paolo Graziano9Marco Castori10Alfredo Scillitani11Vito Guarnieri12Division of Medical Genetics, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyUnit of Endocrinology, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyUnit of Pathology, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyBioinformatic Unit, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyUnit of General Surgery 2nd and Thoracic Surgery, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyLaboratory of Oncology, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyUnit of Endocrinology, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyBioinformatic Unit, Istituto Mendel-CSS, Rome, ItalyUnit of Pathology, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyUnit of Endocrinology, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), ItalyObjective. Atypical parathyroid adenoma is a rare neoplasm, showing atypical histological features intermediate between classic benign adenoma and the rarest parathyroid carcinoma, whose the clinical behaviour and outcome is not yet understood or predictable. Up to date only two cases of atypical adenoma were found associated to a MEN1 syndrome, and only one was proved to carry a pathogenic variant of the MEN1 gene. Design. We report the clinical, histologic, and molecular findings of a 44-year-old woman, presenting with a histologically proved atypical parathyroid adenoma with an apparent aggressive behaviour. Methods and Results. CDC73 gene was screened at germline and somatic levels with no results. Whole exome sequencing performed on DNA extracted from blood leukocytes and tumour tissue revealed a somatic MEN1 gene heterozygous variant, c.912+1G > A, of the splicing donor site of exon 6. On immunohistochemistry, downregulation of the menin protein expression in the neoplastic cells was also observed. Conclusions. We report the second case of a rare association of a somatic MEN1 gene mutation in a patient with atypical parathyroid adenoma. We suggest that MEN1 gene could be an underestimate genetic determinant of these rare histological entities, and we highlight the utility of a complete genetic screening protocol, by the use of next-generation sequencing technology in such undetermined clinical cases with no frank clinical presentation.http://dx.doi.org/10.1155/2020/2080797 |
| spellingShingle | Luigia Cinque Flavia Pugliese Celeste Clemente Stefano Castellana Maria Pia Leone Danilo de Martino Teresa Balsamo Claudia Battista Tommaso Biagini Paolo Graziano Marco Castori Alfredo Scillitani Vito Guarnieri Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma International Journal of Endocrinology |
| title | Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma |
| title_full | Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma |
| title_fullStr | Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma |
| title_full_unstemmed | Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma |
| title_short | Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma |
| title_sort | rare somatic men1 gene pathogenic variant in a patient affected by atypical parathyroid adenoma |
| url | http://dx.doi.org/10.1155/2020/2080797 |
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