Rakheja Dinesh, Boriack Richard L, Mitui Midori, Khokhar Shama, Holt Shelby A, Kapur Payal
Department of Pathology, Children's Medical Center, Dallas, TX, USA.
Tumour Biol. 2011 Apr;32(2):325-33. doi: 10.1007/s13277-010-0125-6. Epub 2010 Nov 16.
Elevated levels of D: -2-hydroxyglutarate (D: -2-HG) occur in gliomas and myeloid leukemias associated with mutations of IDH1 and IDH2. L: -2-Hydroxyglutaric aciduria, an inherited metabolic disorder, predisposes to brain tumors. Therefore, we asked whether sporadic cancers, without IDH1 or IDH2 hot-spot mutations, show elevated 2-hydroxyglutarate levels. We retrieved 15 pairs of frozen papillary thyroid carcinoma (PTC) and adjacent non-neoplastic thyroid, and 14 pairs of hyperplastic nodule (HN) and adjacent non-hyperplastic thyroid. In all lesions, exon 4 sequencing confirmed the absence of known mutations of IDH1 and IDH2. We measured 2-hydroxyglutarate by liquid chromatography-tandem mass spectrometry. Compared to normal thyroid, PTCs had significantly higher D: -2-HG and L: -2-hydroxyglutarate (L: -2-HG) levels, and compared to HNs, PTCs had significantly higher D: -2-HG levels. D: -2-HG/L: -2-HG levels were not significantly different between HNs and normal thyroid. Further studies should clarify if elevated 2-hydroxyglutarate in PTC may be useful as cancer biomarker and evaluate the role of 2-hydroxyglutarate in cancer biology.
与异柠檬酸脱氢酶1（IDH1）和异柠檬酸脱氢酶2（IDH2）突变相关的胶质瘤和髓系白血病中会出现D-2-羟基戊二酸（D-2-HG）水平升高。L-2-羟基戊二酸尿症是一种遗传性代谢紊乱疾病，易引发脑肿瘤。因此，我们探讨了无IDH1或IDH2热点突变的散发性癌症是否表现出2-羟基戊二酸水平升高。我们获取了15对冷冻的乳头状甲状腺癌（PTC）及其相邻的非肿瘤性甲状腺组织，以及14对增生性结节（HN）及其相邻的非增生性甲状腺组织。在所有病变中，第4外显子测序证实不存在IDH1和IDH2的已知突变。我们通过液相色谱-串联质谱法测量2-羟基戊二酸。与正常甲状腺相比，PTC的D-2-HG和L-2-羟基戊二酸（L-2-HG）水平显著更高，与HN相比，PTC的D-2-HG水平显著更高。HN与正常甲状腺之间的D-2-HG/L-2-HG水平无显著差异。进一步的研究应阐明PTC中升高的2-羟基戊二酸是否可用作癌症生物标志物，并评估2-羟基戊二酸在癌症生物学中的作用。
