Molecular genetic analysis of deep-seated glioblastomas

Abstract

Glioblastoma can be divided into genetic subsets. The most prominent criterion for dividing glioblastomas into subsets is the dichotomy between TP53 mutation and EGFR amplification, two genetic alterations that almost never coincide in the same tumor. Approximately one third of glioblastomas have TP53 mutations, one third have EGFR amplification, and one third have neither. When viewed in terms of tumor progression, secondary glioblastomas have a much higher incidence of TP53 mutations than do primary glioblastomas. When viewed in terms of the age of tumor onset, glioblastomas in young adults are likely to have TP53 mutations. However, no correlations have yet been found between the tumor locations and the genetic subsets. In this study, we evaluated the associations between the glioblastoma sites and the genetic subsets defined by the presence of the TP53 mutation or EGFR amplification in nine deep-seated glioblastomas of the thalamus and basal ganglia. All nine tumors were clinically defined as primary glioblastomas. Our investigation revealed that all tumors had TP53 mutations and none had EGFR amplifications. These findings suggest that glioblastomas deep-seated in the thalamus and basal ganglia can be grouped into a subset of glioblastomas with TP53 mutations, akin to the subsets of secondary and younger adult glioblastomas. The locations where the glioblastomas originate may be associated with the genetic features.