Project description
Molecular characterisation of brain tumours
Brain tumours are heterogeneous and, unlike haematopoietic malignancies, the cell of origin is unknown in most cases. BRAIN-MATCH, an EU-funded initiative, aims to understand brain tumour biology by analysing the molecular profiles of normal brain cells at different stages during development at single cell resolution and integrating with thousands of brain tumour datasets that cover more than 100 different brain tumour entities. This integrative approach will help scientists identify the cells of origin for many of these tumours. Project results also have clinical projections and aim at hinting to novel therapies and liquid biopsy-based assays for the detection of tumour cells circulating in the blood.
Objective
Brain tumors represent an extremely heterogeneous group of more than 100 different molecularly distinct diseases, many of which are still almost uniformly lethal despite five decades of clinical trials. In contrast to hematologic malignancies and carcinomas, the cell-of-origin for the vast majority of these entities is unknown. This knowledge gap currently precludes a comprehensive understanding of tumor biology and also limits translational exploitation (e.g. utilizing lineage targets for novel therapies and circulating brain tumor cells for liquid biopsies).
The BRAIN-MATCH project represents an ambitious program to address this challenge and unmet medical need by taking an approach that (i) extensively utilizes existing molecular profiles of more than 30,000 brain tumor samples covering more than 100 different entities, publicly available single-cell sequencing data of normal brain regions, and bulk normal tissue data at different times of development across different species; (ii) generates unprecedented maps of normal human CNS development by using state-of-the art novel technologies; (iii) matches these molecular portraits of normal cell types with tumor datasets in order to identify specific cell-of-origin populations for individual tumor entities; and (iv) validates the most promising cell-of-origin populations and tumor-specific lineage and/or surface markers in vivo.
The expected outputs of BRAIN-MATCH are four-fold: (i) delivery of an unprecedented atlas of human normal CNS development, which will also be of great relevance for diverse fields other than cancer; (ii) functional validation of at least three lineage targets; (iii) isolation and molecular characterization of circulating brain tumor cells from patients´ blood for at least five tumor entities; and (iv) generation of at least three novel mouse models of brain tumor entities for which currently no faithful models exist.
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Funding Scheme
ERC-COG - Consolidator GrantHost institution
69120 Heidelberg
Germany