MEN4 and CDKN1B mutations: the latest of the MEN syndromes

Abstract

Multiple endocrine neoplasia (MEN) refers to a group of autosomal dominant disorders with generally high penetrance that lead to the development of a wide spectrum of endocrine and non-endocrine manifestations. The most frequent among these conditions is MEN type 1 (MEN1), which is caused by germline heterozygous loss-of-function mutations in the tumor suppressor gene MEN1. MEN1 is characterized by primary hyperparathyroidism (PHPT) and functional or nonfunctional pancreatic neuroendocrine tumors and pituitary adenomas. Approximately 10% of patients with familial or sporadic MEN1-like phenotype do not have MEN1 mutations or deletions. Recently, a novel MEN syndrome was discovered, initially in rats (MENX), and later in humans (MEN4), which is caused by germline mutations in the putative tumor suppressor CDKN1B. The most common phenotype of the 19 cases of MEN4 that have been described to date is PHPT followed by pituitary adenomas. Recently, somatic and germline mutations in CDKN1B were also identified in patients with sporadic PHPT, lymphoma, and breast cancer, demonstrating a novel role for CDKN1B as a tumor susceptibility gene for other neoplasms. In this review, we report on the genetic characterization and clinical features of MEN4.

Multiple endocrine neoplasia: an update

“…In MEN4, patients develop MEN1‐associated tumours, including parathyroid tumours and anterior pituitary tumours, which may occur in association with tumours of the kidneys, adrenals and reproductive organs . The most common phenotypic features are parathyroid neoplasia (80% of patients) and pituitary adenomas, which tend to be smaller and less aggressive than MEN1‐associated pituitary adenomas . Pancreatic NET, including gastrinomas, have also been observed in MEN4 with a decreased penetrance compared to MEN1.…”

Pituitary adenoma: a literature review

“…At li kus ty ri mus, bu vo nu sta ty ta, kad ðá sin dro mà su kelia CDKN1B ge no, esan èio 12 chro mo so mos trum po jo peties 13.1 re gio ne, mu ta ci ja. Jis ko duo ja nu ma no mà tu mo ro su pre so riø p27, ku ris da ly vau ja làs te lës cik lo re gu lia ci jo je, sà vei kau da mas su nuo cik li no pri klau so mo mis ki na zë mis [17][18][19]. Kol kas me di ci ni në je li te ra tû ro je ap ra ðy ta tik 19 at ve jø, kai bu vo nu sta ty tos CDKN1B ge no mu ta ci jos, tai gi kli ni ka në ra iki ga lo api bû din ta ir pa tvir tin ta.…”

“…Kol kas me di ci ni në je li te ra tû ro je ap ra ðy ta tik 19 at ve jø, kai bu vo nu sta ty tos CDKN1B ge no mu ta ci jos, tai gi kli ni ka në ra iki ga lo api bû din ta ir pa tvir tin ta. MEN-4 sin dro mui taip pat la bai bû din gas pir mi nis hi per pa ra ti roidiz mas, HA, neu ro en dok ri ni niai ka sos ir dvy li ka pirð tës þar nos na vi kai, ant inks èiø ne op la zi jos [19]. 2016 m. at likto je de La at ir ben dra au to riø stu di jo je bu vo pa ste bë ta, kad ðis sin dro mas pa si reið kia ðiek tiek vë liau ir jo kli ni ki në ei ga ðvel nes në nei MEN-1 sin dro mo [20].…”

Happy 20th anniversary MEN1: from positional cloning to gene function restoration

“…The review articles cover the broad range of MEN1 syndrome and focus on the clinical (Manoharan et al 2017, Marini et al 2017, van Leeuwaarde et al 2017, translational (Agarwal 2017, Alrezk et al 2017 and basic scientific , Feng et al 2017, Mohr & Pellegata 2017 aspects; therefore, they provide a comprehensive update on MEN1. We are delighted that several of the scientists that pioneered MEN1 research provided their expertise to this special issue.…”

“…In their review, the authors outline the genetics, clinical manifestations and management of patients with the closely related MEN4 syndrome, caused by germline mutations in the gene (CDKN1B) coding for p27 that result in the development of parathyroid and pituitary adenomas (Alrezk et al 2017).…”