PTEN (MMAC1) MUTATIONS ARE FREQUENT IN PRIMARY GLIOBLASTOMAS (DE-NOVO) BUT NOT IN SECONDARY GLIOBLASTOMAS

Loss of heterozygosity (LOW) on chromosome 10 is the most frequent gen etic alteration associated with the evolution of malignant astrocytic rumors and it may involve several loci. The tumor suppressor gene PTEN (MMAC1) on chromosome 10q23 is mutated in approximately 30% of gliobl astomas (WHO Grade IV). In this study, we assessed the frequency of PT EN mutations in primary glioblastomas, which developed clinically de n ovo, and in secondary glioblastomas, which evolved from low-grade (WHO Grade II) or anaplastic astrocytomas (WHO Grade ITT). Nine of 28 (32% ) primary glioblastomas contained a PTEN mutation and an additional ca se showed a homozygous PTEN deletion. This indicates that after overex pression/amplification of the EGF receptor, loss of PTEN function is t he most common alteration in primary glioblastomas. In this series, 5 of 28 (18%) primary glioblastomas showed both a PTEN mutation and EGFR amplification. Tn contrast, only 1 of 25 (4%) secondary glioblastomas contained a PTEN mutation, and none of them showed a homozygous PTEN deletion. The secondary glioblastoma with a PTEN mutation developed fr om an anaplastic astrocytoma that already carried the mutation. The ob servation that secondary glioblastomas have a p53 mutation as a geneti c hallmark bur rarely contain a PTEN mutation supports the concept tha t primary and secondary glioblastomas develop differently on a genetic level.