Molecular genetics of radiographically defined de novo glioblastoma multiforme

Glioblastoma multiforme (GBM) represents the final endpoint of anaplastic p rogression in astrocytomas. GBM which arise without clinical evidence of a prior low-grade astrocytoma (LGA) have been designated de novo GBM, and are thought to develop rapidly from initial tumour formation. However, a purel y clinical definition of de novo GBM does not exclude a long-standing, asym ptomatic low-grade tumour. This study therefore sought to determine the gen etic features of a unique group of cases in which GBMs were documented to h ave arisen radiographically in defined period of time (radiographically def ined de novo GBM). Clinical and genetic features were examined in a group o f 11 patients with a histological diagnosis of high-grade astrocytoma at fi rst biopsy and radiographically defined de novo GBM. The mean age of the pa tients at tumour diagnosis was 62 years (range 32-87). Six of 11 tumours ar ose in the temporal lobes. Eight of 11 tumours had epidermal growth factor receptor (EGFR) overexpression, and EGFR gene amplification was found in fi ve of the six analysed cases. Overexpression of p53 was observed in only on e tumour, and a TP53 mutation was present in this case. p16 immunostaining was undetectable in 10 cases, and homozygous deletion of CDKN2A was observe d in four of the six studied tumours. pRb expression was lost in four tumou rs. Mutations in the PTEN gene were detected in two of six cases. The resul ts in this unique group of cases confirms the prior hypothesis that the pro file of genetic alterations in de novo GBM is distinct from that of GBM ari sing from a known LGA, and that these specific genetic pathways promote the rapid development of GBM.