TY - JOUR
T1 - Molecular characteristics and clinical features of multifocal glioblastoma
AU - Dono, Antonio
AU - Wang, Emily
AU - Lopez-Rivera, Victor
AU - Ramesh, Arvind V.
AU - Tandon, Nitin
AU - Ballester, Leomar Y.
AU - Esquenazi, Yoshua
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - EGFR
KW - KDR
KW - Multicentric glioblastoma
KW - Multifocal glioblastoma
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U2 - 10.1007/s11060-020-03539-z
DO - 10.1007/s11060-020-03539-z
M3 - Article
C2 - 32440969
AN - SCOPUS:85085345914
SN - 0167-594X
VL - 148
SP - 389
EP - 397
JO - Journal of neuro-oncology
JF - Journal of neuro-oncology
IS - 2
ER -