Uchino Shinya, Ito Akiko
Dept. of Endocrine Surgery, Noguchi Thyroid Clinic and Hospital Foundation.
Gan To Kagaku Ryoho. 2019 Jul;46(7):1114-1118.
Multiple endocrine neoplasia(MEN)is an autosomal dominantly inherited tumor syndrome which develop tumors in multiple endocrine organs and its subtype, MEN1 and MEN2, are well known. The causative gene for MEN1 is the MEN1 gene located on chromosome 11q13. Primary hyperparathyroidism, pancreatic gastroduodenal neuroendocrine tumor, pituitary tumor, adrenal cortical hyperplasia, or thymic neuroendocrine tumor are the typical features of MEN1 patients. Pathogenic variant of the MEN1 gene is distributed in exons 2-10. The causative gene for MEN2 is the RET gene located on chromosome 10q11.2. MEN2 is characterized by medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. MEN2 is divided into two clinical phenotypes, 2A and 2B. Pathogenic variant of the RET gene concentrated on exons 10, 11, 13-16 and there are strong association of the location of the pathogenic variant with disease phenotype. Recently, it is reported that the pathogenic variant of the CDKN1B gene located on chromosome 12p13 is the cause of MEN4. In this syndrome, MEN1- associated tumors of hyperparathyroidism, pituitary adenomas and neuroendocrine tumors of the pancreas or digestive tract with other endocrine tumors are found. The onset age is relatively high and it shows greater diversity of the tumors compared to MEN1.
多发性内分泌腺瘤病（MEN）是一种常染色体显性遗传肿瘤综合征，可在多个内分泌器官发生肿瘤，其亚型MEN1和MEN2广为人知。MEN1的致病基因是位于11q13染色体上的MEN1基因。原发性甲状旁腺功能亢进、胰腺胃十二指肠神经内分泌肿瘤、垂体瘤、肾上腺皮质增生或胸腺神经内分泌肿瘤是MEN1患者的典型特征。MEN1基因的致病变异分布在外显子2 - 10中。MEN2的致病基因是位于10q11.2染色体上的RET基因。MEN2的特征是甲状腺髓样癌、嗜铬细胞瘤和原发性甲状旁腺功能亢进。MEN2分为两种临床表型，即2A和2B。RET基因的致病变异集中在外显子10、11、13 - 16中，且致病变异的位置与疾病表型有很强的关联。最近有报道称，位于12p13染色体上的CDKN1B基因的致病变异是MEN4的病因。在这种综合征中，可发现与MEN1相关的甲状旁腺功能亢进肿瘤、垂体腺瘤以及胰腺或消化道的神经内分泌肿瘤和其他内分泌肿瘤。发病年龄相对较高，与MEN1相比，肿瘤表现出更大的多样性。
