IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours
IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours
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DOI：
10.1002/path.2913
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发表时间：
2011-07-01
影响因子：
7.3
通讯作者：
Flanagan, Adrienne M.
中科院分区：
文献类型：
--
作者：
Amary, M. Fernanda;Bacsi, Krisztian;Flanagan, Adrienne M.
异柠檬酸脱氢酶1 （IDH1）和IDH2的体细胞突变发生在胶质瘤和急性髓性白血病（AML）中。由于多发性内软骨瘤患者偶尔也有这些情况的报道，我们假设软骨肿瘤也会发生相同的突变。使用Sequenom (R)质谱法筛选了大约1200个间充质肿瘤，包括220个软骨肿瘤，222个骨肉瘤和另一个类似于750个骨和软组织肿瘤的IDH1 R132突变。对IDH1 R132野生型软骨肿瘤和软骨母细胞骨肉瘤进行IDH2 （R172, R140）突变分析。通过毛细管测序和限制性内切酶酶切进行验证。杂合体细胞IDH1/IDH2突变导致潜在的肿瘤代谢物2-羟戊二酸的产生，仅在中央和骨膜软骨肿瘤中检测到，并且在至少56%的这些肿瘤中发现，与R132C所代表的40%相似。该突变等位基因的免疫反应性证实了IDH1 R132H突变。IDH1: IDH2突变比例为10.6:1。未检测到IDH2 R140突变。在单发和多发肿瘤患者中，从内软骨瘤到常规中枢和去分化软骨肉瘤均检测到突变。未检测到种系突变。外周软骨肉瘤和骨软骨瘤未发现突变。总之，IDH1和IDH2突变是常规中央性和骨膜软骨肿瘤中首先发现的常见遗传异常。与胶质瘤和急性髓性白血病一样，这些突变似乎发生在肿瘤发生的早期。我们推测，携带idh突变的细胞的马赛克模式解释了在同一患者中发生不同肿瘤（胶质瘤，AML，多发性软骨肿瘤，血管瘤）的报道。版权所有(C) 2011英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
Somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur in gliomas and acute myeloid leukaemia (AML). Since patients with multiple enchondromas have occasionally been reported to have these conditions, we hypothesized that the same mutations would occur in cartilaginous neoplasms. Approximately 1200 mesenchymal tumours, including 220 cartilaginous tumours, 222 osteosarcomas and another similar to 750 bone and soft tissue tumours, were screened for IDH1 R132 mutations, using Sequenom (R) mass spectrometry. Cartilaginous tumours and chondroblastic osteosarcomas, wild-type for IDH1 R132, were analysed for IDH2 (R172, R140) mutations. Validation was performed by capillary sequencing and restriction enzyme digestion. Heterozygous somatic IDH1/IDH2 mutations, which result in the production of a potential oncometabolite, 2-hydroxyglutarate, were only detected in central and periosteal cartilaginous tumours, and were found in at least 56% of these, similar to 40% of which were represented by R132C. IDH1 R132H mutations were confirmed by immunoreactivity for this mutant allele. The ratio of IDH1: IDH2 mutation was 10.6 : 1. No IDH2 R140 mutations were detected. Mutations were detected in enchondromas through to conventional central and dedifferentiated chondrosarcomas, in patients with both solitary and multiple neoplasms. No germline mutations were detected. No mutations were detected in peripheral chondrosarcomas and osteochondromas. In conclusion, IDH1 and IDH2 mutations represent the first common genetic abnormalities to be identified in conventional central and periosteal cartilaginous tumours. As in gliomas and AML, the mutations appear to occur early in tumourigenesis. We speculate that a mosaic pattern of IDH-mutation-bearing cells explains the reports of diverse tumours (gliomas, AML, multiple cartilaginous neoplasms, haemangiomas) occurring in the same patient. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.