BCAT1 for the Diagnosis and Prognosis of Brain Tumors
DKFZ Deutsches Krebsforschungszentrum
- Assay for the determination of BCAT1 expression for prognosis of a tumor
- High specificity (98%) and sensitivity (100%) for detection of tumors with IDH1 and IDH2 wild-type genes
- The fast and reliable assay can be conducted routinely in diagnostic laboratories
- No need for DNA sequencing or mutation-specific antibodies
Glioblastomas are the most common and most aggressive human malignant brain tumors. Treatment options for glioblastomas and other gliomas include neurosurgical techniques (resection or stereotactic procedures), radiation therapy and chemotherapy.
Knowledge of the diagnostic and prognostic factors is crucial for the selection of the best form of life-prolonging therapy.
Studies have shown that glioma patients harboring an isocitrate dehydrogenase (IDH) 1 or 2 mutation have a better prognosis compared to glioma patients with wild-type IDH1 and IDH2.
DKFZ researchers have demonstrated that gliomas with increased (>3 fold compared to control) branched-chain aminotransferase 1 (BCAT1) expression do not harbor IDH1 or IDH2 mutations and thus have a poor prognosis.
The present invention allows a fast and reliable diagnostic and prognostic classification of tumors based on the activity of branched-chain aminoacid metabolism as reflected by the level or activity of BCAT1.
An immunohistochemical assay for classifying tumors based on differences in the metabolism of branched-chain amino acids has been developed.
So far 81 tumor samples have been analyzed. 100% (35 cases) of the tumors bearing IDH1 and IDH2 mutations and 98% (45 cases) of the tumors with IDH1 and IDH2 wild-type proteins have been correctly classified.
The presented immunohistochemical analysis using an anti-BCAT1 antibody is more specific than immunohistochemical analysis using, e.g. the IDH1-R132H antibody. The developed assay is much faster than DNA sequencing, and no mutation-specific antibody is required. The immunohistochemical analysis of BCAT1 expression can be done routinely in diagnostic laboratories. Even tissue samples with low tumor cell content can be analyzed. The determination of BCAT1 level might allow prognoses to be made for other tumor-related diseases.
The inventors are Bernhard Radlwimmer, Sebastian Barbus, Grischa Toedt, Martje Tönjes, Peter Lichter, (all DKFZ Heidelberg) and Guido Reifenberger, (University Düsseldorf).
An international PCT patent application “Methods for the diagnosis and prognosis of a tumor” (PCT/EP2011/002307) was filed May 9th, 2011.
Publication number: WO2011141153