Molecular pathology of the MEN1 gene
Molecular pathology of the MEN1 gene
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DOI：
10.1196/annals.1294.020
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Marx, SJ
中科院分区：
文献类型：
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作者：
Agarwal, SK;Burns, L;Marx, SJ
在所有综合征中，多发性内分泌瘤1型（MEND）在最多的组织类型中引起肿瘤。大多数肿瘤是激素产生的（例如，甲状旁腺、肠胰腺内分泌、垂体前叶）但有些不是（例如，血管纤维瘤）。MEN 1肿瘤在器官类型、不连续器官的区域和连续器官的亚区域中是多个的。癌症导致晚期死亡; MEN 1癌症没有有效的预防或治愈方法。良性肿瘤的发病率高于恶性肿瘤，两者都是筛查的指标。MEN 1型肿瘤的发病年龄通常早于非遗传性病例。广泛的趋势与非肿瘤性激素过量（例如，婴儿期持续性高胰岛素血症性低血糖）。MEN基因中的大多数生殖系或体细胞突变预测编码的menin的截短或缺失。类似地，肿瘤中11 q13杂合性缺失预测其他MEN拷贝的失活。MEN]体细胞突变在非遗传性MEN 1样肿瘤类型中普遍存在。编译生殖系和体细胞突变几乎没有基因型/表型关系。正常的menin是67 kDa，分布广泛，主要是核。它可能与junD、NF-kB、PEM、SMAD 3、RPA 2、FANCD 2、NM 23 β、非肌肉肌球蛋白重链II-A、GFAP和/或波形蛋白合作。这些合作伙伴还没有澄清menin在正常或肿瘤组织中的途径。动物模型为研究menin通路开辟了途径。果蝇中menin的局部过表达揭示了其与junkinase通路的相互作用。Men 1 +/-小鼠具有稳健的MEN 1;其与人MEN 1最重要的区别是胰岛的显著增生，这是肿瘤前体阶段。
Multiple endocrine neoplasia type 1 (MEND, among all syndromes, causes tumors in the highest number of tissue types. Most of the tumors are hormone producing (e.g., parathyroid, enteropancreatic endocrine, anterior pituitary) but some are not (e.g., angiofibroma). MEN1 tumors are multiple for organ type, for regions of a discontinuous organ, and for subregions of a continuous organ. Cancer contributes to late mortality; there is no effective prevention or cure for MEN1 cancers. Morbidities are more frequent from benign than malignant tumor, and both are indicators for screening. Onset age is usually earlier in a tumor type of MEN1 than of nonhereditary cases. Broad trends contrast with those in nonneoplastic excess of hormones (e.g., persistent hyperinsulinemic hypoglycemia of infancy). Most germline or somatic mutations in the MEN] gene predict truncation or absence of encoded menin. Similarly, 11q13 loss of heterozygosity in tumors predicts inactivation of the other MEN] copy. MEN] somatic mutation is prevalent in nonhereditary, MEN1-like tumor types. Compiled germline and somatic mutations show almost no genotype/phenotype relation. Normal menin is 67 kDa, widespread, and mainly nuclear. It may partner with junD, NF-kB, PEM, SMAD3, RPA2, FANCD2, NM23beta, nonmuscle myosin heavy chain II-A, GFAP, and/or vimentin. These partners have not clarified menin's pathways in normal or tumor tissues. Animal models have opened approaches to menin pathways. Local overexpression of menin in Drosophila reveals its interaction with the junkinase pathway. The Men1+/- mouse has robust MEN1; its most important difference from human MEN1 is marked hyperplasia of pancreatic islets, a tumor precursor stage.