Calender Alain
Service de génétique moléculaire et médicale, hôpital Edouard-Herriot, bâtiment B7, 5, place d'Arsonval, 69437 Lyon 03, France.
Nephrol Ther. 2006 Jan;2 Suppl 2:S127-36.
Multiple endocrine neoplasia (MEN) are major predisposition syndromes to endocrine tumours and are characterised by an autosomal dominant disorder and full penetrance. MEN-1 is a major form of hyperparathyroidism associated with a high prevalence of endocrine tumours of the pancreas, pituitary gland, adrenal cortex and the lymphoid and bronchial endocrine tissues. MEN-2 is the familial syndrome of medullary thyroid carcinoma, associated with pheochromocytoma and hyperparathyroidism. Apart from the clinical expression of their allelic variants, both syndromes are different in their physiopathogenesis, in that MEN-2 is related to the constitutional activation of the proto-oncogene RET that encodes a putative tyrosine kinase receptor, while MEN-1 is a tumour suppressor gene model, related to mutations in the menin adapter-protein of multiple intracellular functions. The study of other rarer forms of predisposition to endocrine tumours, and especially to hyperparathyroidism, has uncovered new genes such as HRPT2, which show that multiple physiological routes, including the close regulation of transcription and genetic stability, may lead to the same clinical outcome. These hereditary models of endocrine cancer contribute as much to further physiopathogenic knowledge as to the therapeutic recommendations for managing these syndromes.
多发性内分泌腺瘤病(MEN)是内分泌肿瘤的主要易感综合征,其特征为常染色体显性遗传病且具有完全外显率。MEN-1是甲状旁腺功能亢进的主要形式,与胰腺、垂体、肾上腺皮质以及淋巴和支气管内分泌组织的内分泌肿瘤高发相关。MEN-2是甲状腺髓样癌的家族性综合征,与嗜铬细胞瘤和甲状旁腺功能亢进相关。除了其等位基因变异的临床表现外,这两种综合征在发病机制上也有所不同,MEN-2与原癌基因RET的组成性激活有关,该基因编码一种假定的酪氨酸激酶受体,而MEN-1是一种肿瘤抑制基因模型,与具有多种细胞内功能的Menin衔接蛋白的突变有关。对其他更罕见的内分泌肿瘤易感形式,尤其是甲状旁腺功能亢进的研究,发现了新的基因,如HRPT2,这表明包括转录的密切调控和遗传稳定性在内的多种生理途径可能导致相同的临床结果。这些内分泌癌的遗传模型对进一步了解发病机制以及对这些综合征的治疗建议都有很大贡献。