期刊
EUROPEAN JOURNAL OF CANCER
卷 90, 期 -, 页码 83-91出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2017.11.024
关键词
Intrahepatic cholangiocarcinomas; Isocitrate dehydrogenase; 2-hydroxyglutarate; Oncometabolite
类别
资金
- Fondation Gustave Roussy (Revolution Cancer initiative) [INCa-DGOS-INSERM 6043]
- MMO [ANR-10-IBHU-0001]
Therapeutic resources are limited for advanced biliary tract cancers and prognosis remains poor. Somatic mutations in isocitrate dehydrogenase (IDH) 1/2 gene are found in 5-36% of patients with intrahepatic cholangiocarcinoma (ICC). The mutant forms of IDH1/2 catalyse the non-reversible accumulation of 2-hydroxyglutarate (2HG). Increasing numbers of indirect or direct-targeted therapies are developed to IDH1/2 mutations and could be assisted by a routinely feasible, rapid and inexpensive serum 2HG measurement by liquid chromatography coupled to tandem mass spectrometry. By comparing eight patients with an IDH1/2-mutated ICC to nine patients with wild-type IDH1/2 ICC, we found significantly higher levels of 2HG in patients with IDH1/2 mutations versus the wild-type group (median, 10.9 vs. 0.8 mmol/L, p = 0.0037). D and L-2HG enantiomer levels significantly differed between the two groups with a higher level of D-2HG (p < 0.0001) in patients with IDH1/2 mutations. Accordingly, the D/L ratio was markedly higher in the patients with IDH1/2 mutations compared with the wild-type group (38.0 vs. 0.9 mu mol/L, p < 0.0001). D-2HG measurement ensured 100% sensitivity and specificity at a cut-off of 0.6 mu mol/L. D-2HG levels were correlated with tumour burden and tumour response to treatment with IDH-targeted therapies or indirect therapies. D-2HG serum level measurement by liquid chromatography coupled to tandem mass spectrometry is a sensitive, specific, precise (a coefficient of variation < 10% and an accuracy > 95%), fast (9 min run per sample) and inexpensive surrogate marker of IDH1/2 somatic mutation in ICC. Systematic measurement in patients with ICC may facilitate access to, and monitoring of, IDH-driven therapies. (C) 2017 Elsevier Ltd. All rights reserved.
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