Validation of proteomic signatures for the in vitro diagnosis of primary lymphoma of the central nervous system

• Applicants: Professor Dr. Uwe Schlegel; Professor Dr. Kai Stühler
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271981689

The aim of the research project is the validation of recently identified protein biomarkers with the help of the largest collection of liquor samples from primary CNS lymphoma (PCNSL) patients in Germany. The ultimate goal of the work is the development of a method for the non-invasive diagnosis of PCNSL. Approximately 2 to 3% of all brain tumors are PCNSL with main occurrence between the 5th and 7th decade of live. PCNSL are malign extranodal lymphoma of the non-Hodgkin type and belong to the B-cell-type. Before the methotrexate based chemotherapy was applied the prognosis of patients with PCNSL was adverse, but was improved with the development of a novel therapy concept in Germany. The early and exact diagnosis of PCNSL is of high importance because of serious neurological damages caused by fast growing PCNSL as an unfavorable initial situation for therapy. It has been shown that for a subgroup of PCNSL patients early treatment of disease lead to curative outcome.The exact differential diagnosis between PCNSL and other tumors as well as inflammatory disease of the brain is the most important aspect in treatment management. At the moment the morphological judgment and immunohistochemical analysis of tissue biopsies is still the gold standard. The biopsy is an invasive method and sometimes due to an unfavorable position of the lesion associated with periprocedural morbidity. Additionally, the reduction of tumor size by steroid treatment often leads to the disqualification of a biopsy. Therefore, new methods allowing diagnosing PCNSL by simple liquor and blood assay are desirable.For the identification of protein biomarkers we successfully performed a phase 1 study. The liquor proteome analysis of 50 PCNSL patients and controls revealed 146 candidate biomarkers. Here, these candidate biomarkers will be validated in a phase 2 study using additional 400 liquor samples. For the successful realization of the project the applicants possess i) the largest liquor biobank of PCNSL patients in Germany, ii) experimental confirmed candidate biomarkers which significantly correlate with PCNSL and functionally linked to the pathogenesis of PCNSL, iii) specific and sensitive mass spectrometric methods and iv) established network with additional productive neurological clinics with a significant number of PCNSL patients.

• DFG Programme: Research Grants