Mutation in the PTEN/MMAC1 gene in archival low grade and high grade gliomas

The PTEN gene, located on 10q23.3, has recently been described as a candida te tumour suppressor gene that may be important in the development of advan ced cancers, including gliomas. We have investigated mutation in the PTEN g ene by direct sequence analysis of PCR products amplified from samples micr odissected from 19 low grade (WHO Grade I and II) and 27 high grade (WHO gr ade III and IV) archival, formalin-fixed, paraffin-embedded gliomas. Eleven genetic Variants in ten tumours have been identified. Eight of these are D NA sequence changes that could affect the encoded protein and were present in 0/2 pilocytic astrocytomas, 0/2 oligoastrocytomas, 0/1 oligodendroglioma , 0/14 astrocytomas, 3/13 (23%) anaplastic astrocytomas and 5/14 (36%) glio blastomas. PTEN mutations were found exclusively in high grade gliomas; thi s finding was statistically significant. Only two of the PTEN genetic varia nts have been reported in other studies; two of the genetic changes are in codons in which mutations have not been found previously. The results of th is study indicate that mutation in the PTEN gene is present only in histolo gically more aggressive gliomas, may be associated with the transition from low histological grade to anaplasia, but is absent from the majority of hi gh grade gliomas.