Genomic determinants of the diffusely infiltrative gliomatosis cerebri phenotype

Purpose: Gliomatosis cerebri (GC) is defined as a diffusely infiltrative pattern of growth affecting at least three contiguous lobes of the brain. GC presents unique challenges in terms of surgery and radiation therapy. We evaluated the genomic determinants of GC. Methods: In this retrospective study, we evaluated genetic alterations and overall (OS) and progression-free survival (PFS) durations in radiographically verified cases of GC (glioblastoma [GBM]-GC or astrocytoma IDH mutant-GC) from 2013 to 2023 and their matched non-GC controls. Results: We identified 63 GC cases (45 GBM-GC and 18 astrocytoma IDH mutant-GC) and 126 matched controls. Statistically significant alterations in telomerase reverse transcriptase (TERT) promoter were found in 68% of the GBM matched controls versus only 38% of the GBM-GC patients (p = 0.002 and false discovery rate (FDR) = 0.04). The same held true for the subgroup of primary GBM-GC (p = 0.002 and FDR = 0.04) but not for secondary GBM-GC. In terms of PFS duration, the GBM-GC patients did not significantly differ from the matched controls (p = 0.720). However, the astrocytoma IDH mutant-GC patients had a shorter PFS duration than did the matched controls (p = 0.036). In terms of OS duration, neither the GBM-GC group nor the astrocytoma, IDH mutant-GC group significantly differed (p = 0.589 and p = 0.39, respectively). None of the genetic alterations in these groups were significantly associated with PFS or OS duration. Conclusions: The lower frequency of TERT promoter mutations in GBM-GC may be a characteristic of primary GBM-GC. GC patients had similar OS durations to those of matched non-GC controls. Further studies are needed to validate these results, given this study’s small sample size and retrospective nature. This study supports further efforts to understand the molecular characteristics of GC and perhaps include patients with GC in more clinical trials.