Section on Endocrinology Genetics, Program on Developmental Endocrinology Genetics, Eunice Kennedy Shriver National Institute of Child Health and Paediatric Endocrinology Inter-Institute Training Program, National Institutes of Health, Bethesda, MD 20892, USA.
Best Pract Res Clin Endocrinol Metab. 2010 Jun;24(3):439-49. doi: 10.1016/j.beem.2010.02.002.
Neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex (TSC) are two familial syndromes known as phakomatoses that may be associated with endocrine tumours. These hereditary cutaneous conditions affect the central nervous system and are characterised by the development of hamartomas. Over the past 20 years, there have been major advances in our understanding of the molecular basis of these diseases. Both NF-1 and TSC are disorders of unregulated progression through the cell cycle, in which causative genes behave as tumour suppressor genes. The pathogenesis of these familial syndromes is linked by the shared regulation of a common pathway, the protein kinase mammalian target of rapamycin (mTOR). Additional related disorders that also converge on the mTOR pathway include Peutz-Jeghers syndrome and Cowden syndrome. All of these inherited cancer syndromes are associated with characteristic skin findings that offer a clue to their recognition and treatment. The discovery of mTOR inhibitors has led to a possible new therapeutic modality for patients with endocrine tumours as part of these familial syndromes.
神经纤维瘤病 1 型（NF-1）和结节性硬化症复合征（TSC）是两种被称为“Phakomatoses”的家族性综合征，可能与内分泌肿瘤有关。这些遗传性皮肤疾病影响中枢神经系统，其特征是错构瘤的发展。在过去的 20 年中，我们对这些疾病的分子基础有了重大的认识进展。NF-1 和 TSC 都是细胞周期失控进展的疾病，其中致病基因表现为肿瘤抑制基因。这些家族性综合征的发病机制通过共同的调节途径（哺乳动物雷帕霉素靶蛋白（mTOR）的蛋白激酶）联系在一起。其他与 mTOR 途径相关的相关疾病包括 Peutz-Jeghers 综合征和 Cowden 综合征。所有这些遗传性癌症综合征都与特征性皮肤表现有关，这些表现为识别和治疗提供了线索。mTOR 抑制剂的发现为这些家族性综合征中患有内分泌肿瘤的患者提供了一种新的治疗方法。
