Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2
Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2
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DOI：
10.1038/ng.994
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发表时间：
2011-12-01
期刊：
影响因子：
30.8
通讯作者：
Flanagan, Adrienne M.
中科院分区：
文献类型：
--
作者：
Amary, M. Fernanda;Damato, Stephen;Flanagan, Adrienne M.
Ollier病和Maffucci综合征的特征是多发性中央软骨肿瘤，在Maffucci综合征中伴有软组织血管瘤。我们发现，在40名患有这些综合征的患者中，有37名患者至少有一个肿瘤在异柠檬酸脱氢酶1（IDH1）或IDH2中发生突变，其中65%导致蛋白质中的R132C取代。在分析的19名患有一种以上肿瘤的个体中，有18名来自给定个体的所有肿瘤都具有影响Arg132的相同IDH1突变。在12例受试者中的2例中，在非肿瘤组织中鉴定出低水平的突变DNA。在一系列中央软骨和血管肿瘤中测量代谢物2HG的水平，包括来自综合征和非综合征受试者的样品，这些水平与IDH1突变的存在强烈相关。这些发现与IDH1或IDH2突变代表这些综合征患者早期合子后发生的模型一致。
Ollier disease and Maffucci syndrome are characterized by multiple central cartilaginous tumors that are accompanied by soft tissue hemangiomas in Maffucci syndrome. We show that in 37 of 40 individuals with these syndromes, at least one tumor has a mutation in isocitrate dehydrogenase 1 (IDH1) or in IDH2, 65% of which result in a R132C substitution in the protein. In 18 of 19 individuals with more than one tumor analyzed, all tumors from a given individual shared the same IDH1 mutation affecting Arg132. In 2 of 12 subjects, a low level of mutated DNA was identified in non-neoplastic tissue. The levels of the metabolite 2HG were measured in a series of central cartilaginous and vascular tumors, including samples from syndromic and nonsyndromic subjects, and these levels correlated strongly with the presence of IDH1 mutations. The findings are compatible with a model in which IDH1 or IDH2 mutations represent early post-zygotic occurrences in individuals with these syndromes.