Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for endocrinology, gastroenterology, surgery, radiology, genetics, and molecular biology specialists. There have been 2 major clinical practice guidance papers published in the past 2 decades, with the most recent published 8 years ago. Since then, several new insights on the basic biology and clinical features of MEN1 have appeared in the literature, and those data are discussed in this review. The genetic and molecular interactions of the MEN1-encoded protein menin with transcription factors and chromatin-modifying proteins in cell signaling pathways mediated by transforming growth factor β/bone morphogenetic protein, a few nuclear receptors, Wnt/β-catenin, and Hedgehog, and preclinical studies in mouse models have facilitated the understanding of the pathogenesis of MEN1-associated tumors and potential pharmacological interventions. The advancements in genetic diagnosis have offered a chance to recognize MEN1-related conditions in germline MEN1 mutation–negative patients. There is rapidly accumulating knowledge about clinical presentation in children, adolescents, and pregnancy that is translatable into the management of these very fragile patients. The discoveries about the genetic and molecular signatures of sporadic neuroendocrine tumors support the development of clinical trials with novel targeted therapies, along with advancements in diagnostic tools and surgical approaches. Finally, quality of life studies in patients affected by MEN1 and related conditions represent an effort necessary to develop a pharmacoeconomic interpretation of the problem. Because advances are being made both broadly and in focused areas, this timely review presents and discusses those studies collectively.

中文翻译：

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多发性内分泌肿瘤 1 型：最新见解

多发性内分泌肿瘤 1 型 (MEN1) 是一种以常染色体显性遗传模式遗传的罕见肿瘤综合征，继续引起内分泌学、胃肠病学、外科、放射学、遗传学和分子生物学专家的极大兴趣。在过去的 2 年中，发表了 2 篇主要的临床实践指导论文，最近的一篇发表于 8 年前。从那时起，文献中出现了一些关于 MEN1 基本生物学和临床特征的新见解，这些数据在本综述中进行了讨论。MEN1的遗传和分子相互作用-编码蛋白menin，在细胞信号通路中具有转录因子和染色质修饰蛋白，由转化生长因子β/骨形态发生蛋白、一些核受体、Wnt/β-连环蛋白和 Hedgehog 介导，小鼠模型中的临床前研究促进了了解 MEN1 相关肿瘤的发病机制和潜在的药理学干预措施。基因诊断的进步为识别生殖系MEN1中的 MEN1 相关疾病提供了机会突变阴性患者。关于儿童、青少年和妊娠临床表现的知识正在迅速积累，这些知识可以转化为这些非常脆弱的患者的管理。关于散发性神经内分泌肿瘤的遗传和分子特征的发现支持了新型靶向疗法的临床试验的发展，以及诊断工具和手术方法的进步。最后，对受 MEN1 和相关疾病影响的患者的生活质量研究代表了开发对该问题的药物经济学解释所必需的努力。由于在广泛和重点领域都取得了进展，因此本次及时的审查提出并集体讨论了这些研究。