Analysis of TP53 and PTEN in gliomatosis cerebri

Gliomatosis cerebri (GC) is a rare glial neoplasm with extensive diffuse brain infiltration but relative preservation of the underlying architecture. Previous molecular studies, mostly analyzing biopsy samples, have suggested an astrocytic origin of GC, but a larger collective of autopsy tissue has not been investigated so far. Furthermore, whether the widespread neoplastic infiltration is based on a monoclonal process is still a matter of debate. In the present study, we screened paraffin-embedded brain tissue from different areas of 18 cases (8 autopsy cases and 10 biopsies) for alterations in the TP53 and PTEN genes. Nuclear accumulation of p53 protein was detected in 9 cases (50%). Somatic TP53 mutations occurred in two autopsy cases (11% of all cases). In the first case, a C→T transition in codon 273 (Arg→Cys) was detected in all tumor samples. In the second case, in tumor samples from one hemisphere, nuclear accumulation of p53 was caused by a G→A transition in codon 244 (Gly→Asp). In the present series, no mutations within the coding region of PTEN were found. Pten expression was observed in two autopsy cases (25%) and seven biopsy samples (70%). These data suggest that TP53 is affected in some cases, but other yet-unidentified genetic alterations might contribute to tumorigenesis in GC. Furthermore, although GC might be a monoclonal process, the presence of different tumor clones cannot be ruled out.