Abstract | PURPOSE: EXPERIMENTAL DESIGN: We initially measured serum 2HG concentration in blood samples collected from 31 patients with intrahepatic cholangiocarcinoma in a screening cohort. Findings were validated across 38 resected patients with intrahepatic cholangiocarcinoma from a second cohort with tumor volume measures. Circulating levels of 2HG were evaluated relative to IDH1/2 mutational status, tumor burden, and a number of clinical variables. RESULTS: Circulating levels of 2HG in the screening cohort were significantly elevated in patients with IDH1/2-mutant (median, 478 ng/mL) versus IDH1/2-wild-type (median, 118 ng/mL) tumors (P < 0.001). This significance was maintained in the validation cohort (343 ng/mL vs. 55 ng/mL, P < 0.0001) and levels of 2HG directly correlated with tumor burden in IDH1/2-mutant cases (P < 0.05). Serum 2HG levels ≥170 ng/mL could predict the presence of an IDH1/2 mutation with a sensitivity of 83% and a specificity of 90%. No differences were noted between the allelic variants IDH1 or IDH2 in regard to the levels of circulating 2HG. CONCLUSIONS: This study indicates that circulating 2HG may be a surrogate biomarker of IDH1 or IDH2 mutation status in intrahepatic cholangiocarcinoma and that circulating 2HG levels may correlate directly with tumor burden. Clin Cancer Res; 20(7); 1884-90. ©2014 AACR.
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Authors | Darrell R Borger, Lipika Goyal, Thomas Yau, Ronnie T Poon, Marek Ancukiewicz, Vikram Deshpande, David C Christiani, Hannah M Liebman, Hua Yang, Hyeryun Kim, Katharine Yen, Jason E Faris, A John Iafrate, Eunice L Kwak, Jeffrey W Clark, Jill N Allen, Lawrence S Blaszkowsky, Janet E Murphy, Supriya K Saha, Theodore S Hong, Jennifer Y Wo, Cristina R Ferrone, Kenneth K Tanabe, Nabeel Bardeesy, Kimberly S Straley, Sam Agresta, David P Schenkein, Leif W Ellisen, David P Ryan, Andrew X Zhu |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 20
Issue 7
Pg. 1884-90
(Apr 01 2014)
ISSN: 1557-3265 [Electronic] United States |
PMID | 24478380
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Biomarkers, Tumor
- Glutarates
- alpha-hydroxyglutarate
- IDH2 protein, human
- Isocitrate Dehydrogenase
- IDH1 protein, human
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Topics |
- Adult
- Aged
- Bile Duct Neoplasms
(blood, genetics, pathology)
- Bile Ducts, Intrahepatic
(pathology)
- Biomarkers, Tumor
(blood)
- Cholangiocarcinoma
(blood, genetics, pathology)
- Female
- Glutarates
(blood)
- Humans
- Isocitrate Dehydrogenase
(blood, genetics)
- Male
- Middle Aged
- Mutation
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