Molecular alterations detected on patients with glioblastoma and low-grade glioma: Review of 37 cases.

Abstract

e15030 Background: Glioblastoma (GBM) is a short term life-threatening tumor, while lower-grade glioma (LGG) is a heterogeneous entity with longer survival due to its natural history. As few therapeutic options emerged in the past decades, innovation is lead by targetable molecular alterations such as FGFR, BRAF, NTRK... Therefore, molecular profiling access is critical for patients. Methods: We collected data from patients with GBM and LGG whose tumor sample underwent a molecular profiling with Foundation Medicine FMI testing trough clinical trials. Results: In the GBM group, we identified 26 patients, 18 males and 8 females. Medium age was 47. Median OS was 20.3 months (IC 95% 14.3-26.2). All patients were IDH wide type, one had a methylated MGMT with 13 unknown. Among them, we identified 126 alterations. The most frequent were: AKT (15.4%), BARD1 (15.4%), CDKN2A (28.5%), CDKN2B (42.3%), CKDN2C (7%), FAM (15.4%), kit (23.1%); MLL (30.7%), MTAP (loss 30.7%,) NF1 (30.7%), NOTCH (23.1%), PDGFRA (26.9%), RB1 (23.1%), tp53 (53.8%). PTEN alteration was present in 13 patients with 3 of them with 2 alterations. EGFR was found with more than 1 alteration in 5 patients: 10 amplifications, 2 rearrangements, 6 deletion and 14 other mutation. Finally, we identified also: 1 patient with a mutation of RET, 2 patients with non-actionable NTRK mutations, 3 MDM2 mutated patients. Two patients with an FGFR alteration underwent a treatment with Erdafitinib. In the LGG group we identified 11 patients, 7 females, with a medium age of 34 years old; median OS was 116.8 months/ 9.6 years (CI 95% 45.8-187.8). All patients were IDH mutated, 2 of them with a IDH2 alteration. 1p19q codeletion was detected in 3 patients with 5 unknown; 1 patent was found to have an MGMT methylation, 8 were not tested. A total of 81 mutations were identified with the most frequent: ATRX (54.5%), CDKN2A (18.1%), EGFR (36.4%) with 2 amplifications and 2 rearrangement; TERT (36.4%), tp53 (54.4%), TSC, NOTCH and PTEN loss in 27.7%. One of the patient has a TMB high (117) and he received immunotherapy in a clinical trial. Each of thr 36 patients had at least 6 mutations. We don’t know the percentage of patients who underwent a molecular profile without any alteration founded. Targetable drivers with a clinical relevance were: FGFR, NTRK, ALK, PTEN, MDM2, CDKN2A and CDKN2B. Conclusions: Molecular profiling gives an important data collection and therapeutic options on poor prognostic tumors such as GBM and LGG and may lead to explore new pathways of innovations.