Molecular characteristics and clinical features of multifocal glioblastoma

• Published in: Journal of neuro-oncology 2020-06, Vol.148 (2), p.389-397
• Main Authors: Dono, Antonio, Wang, Emily, Lopez-Rivera, Victor, Ramesh, Arvind V., Tandon, Nitin, Ballester, Leomar Y., Esquenazi, Yoshua
• Format: Article
• Language: English
• Subjects: Aged; Astrocytoma; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Clinical Study; Demography; Epidermal growth factor receptors; Female; Glioblastoma; Glioblastoma - genetics; Glioblastoma - pathology; Glioma; High-Throughput Nucleotide Sequencing; Humans; Immunoglobulins; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Neurology; Next-generation sequencing; Oncology; Phenotypes; PTEN protein; Retrospective Studies; Statistical analysis; Survival
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-020-03539-z

Introduction Glioblastomas (GBMs) usually occur as a solitary lesion; however, about 0.5–35% present with multiple lesions (M-GBM). The genetic landscape of GBMs have been thoroughly investigated; nevertheless, differences between M-GBM and single-foci GBM (S-GBM) remains unclear. The present study aimed to determine differences in clinical and molecular characteristics between M-GBM and S-GBM. Methods A retrospective review of multifocal/multicentric infiltrative gliomas (M-IG) from our institutional database was performed. Demographics, clinical, radiological, and genetic features were obtained and compared between M-GBM IDH-wild type (IDH-WT) vs 193 S-GBM IDH-WT. Mutations were examined by a targeted next-generation sequencing assay interrogating 315 genes. Results 33M-IG were identified from which 94% were diagnosed as M-GBM IDH-WT, the remaining 6% were diagnosed as astrocytomas IDH-mutant. M-GBM and S-GBM comparison revealed that EGFR alterations were more frequent in M-GBM (65% vs 42% p = 0.019). Furthermore, concomitant EGFR / PTEN alterations were more common in M-GBM vs. S-GBM (36% vs 19%) as well as compared to TCGA (21%). No statistically significant differences in overall survival were observed between M-GBM and S-GBM; however, within the M-GBM cohort, patients harboring KDR alterations had a worse survival ( KDR- altered 6.7 vs KDR- WT 16.6 months, p  = 0.038). Conclusions The results of the present study demonstrate that M-GBM genetically resembles S-GBM, however, M-GBM harbor higher frequency of EGFR alterations and co-occurrence of EGFR / PTEN alterations, which may account for their highly malignant and invasive phenotype. Further study of genetic alterations including differences between multifocal and multicentric GBMs are warranted, which may identify potential targets for this aggressive tumor.