Evaluation of molecular genetic alterations associated with tumor progression in a case of gliomatosis cerebri

Gliomatosis cerebri (GC) is a rare tumor characterized by widespread infiltration of the brain and spinal cord. Although GC usually demonstrates histomorphological features of a low-grade tumor, the formation of secondary highly malignant tumor regions may occur. In order to reveal molecular genetic changes associated with tumor progression in GC, we analyzed factors known to be associated with malignant progression in common astocytomas in an unusual GC case of an 18-year-old patient suffering from this disease for almost 7 years. We detected allelic losses in the Rb gene and in exon 4 of the TP53 gene in a tumor region corresponding to a glioblastoma multiforme. EGFR or MDM2 gene amplifications were absent, and no PTEN mutation or allelic loss on chromosome 10 could be detected. Moreover, compared to tumor-free brain tissue of this patient, tumor regions showed increased EGFR expression. These findings show that malignant progression in GC might be associated with the acquisition of molecular genetic changes also found in low-grade astrocytomas with progression to secondary glioblastoma. These data support the notion that GC can be regarded as a subtype of a common astrocytoma.