Project description:Here we present a novel example of genetic heterogeneity in human malignant brain tumors, in which multiple closely-related driver genes are amplified and activated simultaneously in adjacent intermingled cells. We have observed up to 3 different receptor tyrosine kinases (EGFR, MET, PDGFRA) amplified in single tumors in different cells in a mutually exclusive fashion. However, these subpopulations cannot be always observed with a genome wide studies such as aCGH. Here we include aCGH on three such mosaic cases. Analyses were performed on 350 archival specimens of glioblastoma, WHO Grade IV, seen at the Department of Pathology, Massachusetts General Hospital from 2009 to 2011. CGH on three such mosaic cases.
Project description:Amplification of the epidermal growth factor receptor (EGFR, A0 for non-amplified and A1 for amplified) gene is one of the most common oncogenic alterations in glioblastoma (45%) making it a prime target for therapy. However, small molecule inhibitors of the EGFR tyrosine kinase showed disappointing efficacy in clinical trials for glioblastoma. Here we report expression data for 33 samples including 6 GBM derived xenografts (3 controls and 3 treated by tyrosine kinase inhibitor gefitinib) and 27 glioblastoma tumors (11 controls and 16 treated by tyrosine kinase inhibitor gefitinib). Note that T0, T1 and T2 treatment types mean that control, Gefitinib treatment and Gefitinib treatment (but not according to protocol schedule), respectively.
Project description:Here we present a novel example of genetic heterogeneity in human malignant brain tumors, in which multiple closely-related driver genes are amplified and activated simultaneously in adjacent intermingled cells. We have observed up to 3 different receptor tyrosine kinases (EGFR, MET, PDGFRA) amplified in single tumors in different cells in a mutually exclusive fashion. However, these subpopulations cannot be always observed with a genome wide studies such as aCGH. Here we include aCGH on three such mosaic cases. Analyses were performed on 350 archival specimens of glioblastoma, WHO Grade IV, seen at the Department of Pathology, Massachusetts General Hospital from 2009 to 2011.
