BioProject

Background: Glioblastoma (GBM) is the deadliest primary brain cancer in adults. More...

Background: Glioblastoma (GBM) is the deadliest primary brain cancer in adults. Emerging innovative therapies hold promise for personalized cancer treatment. Improving therapeutic options depends on research relying on relevant preclinical models. In this line we have established in the setting of the GlioTex project (GBM and experimental therapeutics), a GBM-patient derived cell line library (GBM-PDCL). Multi-OMIC approach was used to determine the molecular landscape of PDCL and the extent to which they represent GBM tumors.Methods: SNP-array, expression arrays, exome sequencing and RNA sequencing were used to measure and compare the molecular landscapes of 20 samples representing ten human GBM and paired GBM-PDCL.Results: Copy number variations were similar for a median of 85% of the genome and for 59% of the major focal events. Somatic point mutations were similar in a median of 41%. Mutations in GBM driver and “druggable” genes were maintained in 67% events. Mutations that were not conserved in the PDCL were mainly low allelic fraction and/or non-driver mutations. Based on RNA expression profiling, PDCL cluster closely to their parental tumor with overexpression of pathways associated with cancer progression in PDCL. Conclusions: Overall, PDCL recapitulate pivotal molecular alterations of paired-parental tumors supporting their use as preclinical model of GBM. However, some driver aberrations are lost or gained in the passage from tumor to PDCL. Our results support using PDCL as relevant preclinical model of GBM. Further investigations of changes between PDCL and their parental tumor may provide insights in GBM biology. Less...