biostudies-literaturePiccirillo SGCancer Research UKMedical Research CouncilNational Institute for Health Research (NIHR)The Brain Tumour CharityWellcome Trust194-202https://www.ebi.ac.uk/biostudies/studies/S-EPMC4286248biostudies-literatureUnknown75(1)Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity and treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in the sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis and genomic characterization revealed that the SEZ harbors malignant cells with tumor-initiating capacity, analogous to cells isolated from the fluorescent tumor mass (T). We observed resistance to supramaximal chemotherapy doses along with differential patterns of drug response between T and SEZ in the same tumor. Our results reveal novel insights into glioblastoma growth dynamics, with implications for understanding and limiting treatment resistance.Cancer researchContributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone.PMC4286248C1023/A1454519556G1001522NIHR/CS/009/011A14545090340MC_UU_12022/1A10825C14303/A10825MC_UU_12022/810/1361670014545Venkitaraman ARSpiteri ICurtis CCollins VPPiccirillo SGWatts CFrancis NJBer SHeywood RHowarth KDTouloumis ASottoriva ATavare SMarioni JCPrice SJfalseContributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone.Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity and treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in the sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis and genomic characterization revealed that the SEZ harbors malignant cells with tumor-initiating capacity, analogous to cells isolated from the fluorescent tumor mass (T). We observed resistance to supramaximal chemotherapy doses along with differential patterns of drug response between T and SEZ in the same tumor. Our results reveal novel insights into glioblastoma growth dynamics, with implications for understanding and limiting treatment resistance.2015-01-01T00:00:00Z2015 Jan2026-04-29T12:28:11.869Z2019-03-27T01:42:53ZS-EPMC42862482540619310.1158/0008-5472.can-13-313110.1158/0008-5472.CAN-13-3131