Clinically Actionable Insights Into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches

摘要: Glioblastoma is the most common primary adult brain tumour, and despite optimal treatment, median survival 12–15 months. Patients with matched recurrent glioblastomas were investigated to try find actionable mutations. Tumours profiled using a validated DNA-based gene panel. Copy number variations (CNVs) single nucleotide variants (SNVs) examined, potentially pathogenic clinically mutations identified. The results revealed that IDH-wildtype (IDHWT; n = 38) IDH-mutant (IDHMUT; n = 3). SNVs in TSC2, MSH6, TP53, CREBBP, IDH1 of unknown significance (VUS) predicted be both subtypes. IDHWT tumours had impacted RTK/Ras/PI(3)K, p53, WNT, SHH, NOTCH, Rb, G-protein pathways. Many BRCA1/2 (18%) variants, including confirmed somatic haemangioblastoma. fewer pathways (RTK/Ras/PI(3)K, G-protein) CNV gains (BRCA2, GNAS, EGFR) losses (TERT SMARCA4). IDHMUT WNT VUS KLK1 was possibly IDHMUT. Recurrent also (p53, by genetic alterations. Public datasets (TCGA GDC) clinical findings Overall this cohort, variation often identified EGFR, PTEN, BRCA1/2, ATM. This study underlines need for detailed molecular profiling identify individual GBM patients who may eligible novel treatment approaches. information crucial patient recruitment trials.