The future: diagnostic and imaging advances in MEN1 therapeutic approaches and management strategies

Manoharan, Jerena; Albers, Max B.; Bartsch, Detlef K.

doi:10.1530/erc-17-0231

Cited by 27 publications

(22 citation statements)

References 144 publications

(152 reference statements)

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“…Of note, maternal imprinting with silencing of the maternal allele occurs for SDHD and SDHAF2, and thus, only mutations inherited from the father will cause disease [10,11]. Some of the genetic syndromes associated with PPGL can be diagnosed based on clinical criteria [Multiple Endocrine Neoplasia type 2 (MEN2), Von Hippel Lindau syndrome (VHL), Neurofibromatosis type 1 (NF1), Multiple Endocrine Neoplasia type (MEN1) and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome (HLRCC)], see Table 1 [12][13][14][15][16][17][18], and recommendations for the surveillance of healthy carriers of pathogenic variants in these syndromes are already published [19][20][21][22][23][24][25][26][27][28][29][30][31], Table 2. Surveillance recommendations were lacking at the initiation of this work for genes discovered from year 2000 and onwards: SDHA, SDHB, SHDC, SDHD, SDHAF2 (together abbreviated SDHx), as well as TMEM127, and MAX [10,[32][33][34][35][36][37][38].…”

Section: Introduction and Epidemiologymentioning

confidence: 99%

Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

et al. 2019

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Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first‐degree relatives (and second‐degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy‐catecholamines and bi‐annual rapid whole‐body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre‐symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow‐up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.

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Section: Introduction and Epidemiologymentioning

confidence: 99%

Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

et al. 2019

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“…place in diagnosis, and in particular, imaging of MEN1-associated tumors (Manoharan et al 2017). The authors discuss the modalities and timing for MEN1 surveillance and highlight the development and importance of novel imaging techniques.…”

Section: :10mentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Weber¹,

Mulligan²

2017

Endocrine-Related Cancer

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“…Unfortunately, all these treatment options only lead to tumor growth stabilization. Regular screening examinations are advised for MEN1 patients to detect NENs, especially pNENs, as early as possible [1,7].…”

Section: Introductionmentioning

confidence: 99%

Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model

et al. 2018

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Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few chemopreventive strategies (e.g., with somatostatin analogues) have been evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1^(+/T) knockout mice, the effect of aspirin (n = 25) and an inhibitor of angiotensin-I converting enzyme (enalapril, n = 25) compared to controls (n = 25) were evaluated as single chemopreventive strategies for pNENs after 6, 9, 12, 15, and 18 months. After each study period, mice were sacrificed and the resected pancreata were evaluated by histopathological analysis, immunostaining, and real-time PCR. PNEN size and number was measured. Aspirin and enalapril lead to a pNEN size reduction of 80% (167,518 vs. 838,876 µm², p < 0.001) and 79% (174,758 vs. 838,876 µm², p < 0.001) compared to controls. Furthermore, aspirin and enalapril treatment resulted in a significant reduction of the number of pNENs by 33%, (p = 0.04) and 41% (p = 0.002) respectively. The apoptosis marker caspase 3 revealed a higher positive expression in pNEN of treated Men1^(+/T) mice. Immunostaining of VEGF in pNEN detected a downregulation of its expression in treated Men1^(+/T) mice compared to the control group. REL A transcript was significantly downregulated in 18-months treated enalapril Men1^(+/T) mice, but not in aspirin-treated Men1^(+/T) mice. There was no significant difference in the Ki-67 index. Using a transgenic mouse model that imitates human MEN1, this study provides first evidence that aspirin and enalapril are effective chemopreventive agents that aid in the progression of pNENs.

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The future: diagnostic and imaging advances in MEN1 therapeutic approaches and management strategies

Cited by 27 publications

References 144 publications

Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

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

Chemoprevention with Enalapril and Aspirin in <b><i>Men1</i></b><sup><i>(+/T)</i></sup> Knockout Mouse Model

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