Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes

The current WHO classification of brain tumors defines gliomatosis cerebri (GC) as an extensively infiltrating astrocytic glioma involving at least three cerebral lobes. The relation of GC to diffuse astrocytomas and glioblastoma is uncertain. Due to malignant biological behavior, GC is allotted to WHO grade III. Recent reports showed IDH1 mutations in astrocytic and oligodendroglial tumors WHO grades II and III and in secondary glioblastomas with a frequency of up to 90%, whereas IDH1 mutations occurred in only 5% of primary glioblastomas. Here, we examined the frequency of IDH1 mutations in 35 GC samples by direct sequencing, derived cleaved amplified polymorphic sequence analysis and immunohistochemistry. We identified IDH1 mutations in 10/24 (42%) cases, which also included a solid tumor portion (type 2 GC), but not in 11 classical cases without solid tumor mass (type 1 GC). TP53 mutations were revealed in two type 2 GC, but not in any type 1 GC, while combined chromosomal losses of 1p and 19q were not found at all. Our data suggest that GC consists of two histological/molecular subtypes, type 1 being clearly distinct from diffuse astrocytoma, and type 2 sharing features with diffuse astrocytoma.