文章：

1型和2型多发性内分泌肿瘤的分子遗传学研究

Molecular genetics of multiple endocrine neoplasia types 1 and 2

原文发布日期：2005-05-01

DOI: 10.1038/nrc1610

类型: Review Article

开放获取: 否

要点：

1. Multiple endocrine neoplasia (MEN) type 1 (MEN1) and MEN type 2 (MEN2) are the most striking MEN syndromes in terms of hormonal excesses. They differ in that both are potentially lethal from associated cancer but only MEN2-related cancer can be prevented. Similar names cause confusion between them.
2. MEN1 sequencing gives useful information about the MEN1 carrier status. This test is not a clinical requirement for relatives of individuals with MEN1 as it is not a major guide for therapy.
3. Men1^+/− mice are a good model of MEN1. Features that differ from MEN1 loss in man include a higher penetrance of pheochromocytoma and a stage of polyclonal hyperplasia in pancreatic islet cells as the precursor to insulinoma.
4. RET mutations cause three variants of MEN2 with three grades of calcitonin-producingcell (C-cell) cancer and with a strong correlation of RET genotype to phenotype.
5. RET sequencing is recommended in relatives of individuals with MEN2 as a guide for the successful management for C-cell cancer and pheochromocytoma.
6. Tumorigenesis after mutation of MEN1 (a tumour suppressor) follows a typical twohit loss-of-function process.
7. Tumorigenesis after mutation of RET (an oncogene) follows a stepwise process; sometimes this involves a second hit in a RET allele. This probably causes further imbalance towards RET gain of function.
8. The roles of menin (the protein encoded by MEN1) in tumorigenesis are obscured by its large number of candidate partners and candidate physiologies. A specific anti-MEN1 drug cannot be contemplated until MEN1 function is better understood.
9. RET mutations are oncogenic owing to a gain of function in RET's intrinsic receptor tyrosine kinase activity. Tyrosine-kinase inhibitors are in clinical trials for RET-related neoplasms.

要点翻译：

1. 多发性内分泌腺瘤病（MEN）1型（MEN1）和2型（MEN2）是激素过量表现最为显著的MEN综合征。两者的区别在于：虽然均可能因相关癌症致命，但仅MEN2相关癌症可被预防。相似的命名常引起混淆。
2. MEN1基因测序可提供有价值的MEN1携带状态信息。该检测并非MEN1患者亲属的临床必需项目，因其对治疗方案的指导作用有限。
3. Men1+/−小鼠是理想的MEN1疾病模型。与人类MEN1功能缺失的不同之处包括：更高的嗜铬细胞瘤外显率，以及胰岛细胞多克隆增生阶段作为胰岛素瘤的前驱表现。
4. RET基因突变导致MEN2的三种变异型，其降钙素生成细胞（C-细胞）癌变程度分为三级，且RET基因型与表型存在强相关性。
5. 推荐对MEN2患者亲属进行RET基因测序，以指导C-细胞癌和嗜铬细胞瘤的成功管理。
6. MEN1（抑癌基因）突变后的肿瘤发生遵循典型的二次打击功能缺失过程。
7. RET（原癌基因）突变后的肿瘤发生呈渐进式过程；有时涉及RET等位基因的二次打击。这可能导致RET功能获得性失衡加剧。
8. menin蛋白（由MEN1基因编码）在肿瘤发生中的作用因其大量候选相互作用蛋白和生理功能而难以明晰。唯有在更好理解MEN1功能后，才能考虑开发特异性抗MEN1药物。
9. RET突变通过增强其内在受体酪氨酸激酶活性功能而致癌。针对RET相关肿瘤的酪氨酸激酶抑制剂已进入临床试验阶段。

英文摘要：

Six multiple endocrine neoplasia (MEN) syndromes have received a level of attention that might seem disproportionate to their low prevalence. The attention has been given because their hormonal excesses cause striking metabolic expressions and because they might clarify pathways disrupted in more common tumours. The recent discovery of the main gene in each MEN syndrome has furthered our understanding of not only hereditary but also sporadic tumours and has fostered new avenues of research.

摘要翻译： 

六种多发性内分泌腺瘤（MEN）综合征所受到的关注程度，似乎与其低患病率并不相称。之所以备受关注，是因为其激素过量会引起显著的代谢表现，并可能揭示更常见肿瘤中被破坏的信号通路。近期，每种MEN综合征主要致病基因的发现，不仅加深了我们对遗传性肿瘤的理解，也推动了对散发性肿瘤的研究，并开辟了新的研究方向。

原文链接：

Molecular genetics of multiple endocrine neoplasia types 1 and 2