Mutational Analysis of the PTEN/MMAC1 Tumor Suppressor Gene in Sporadic Glioblastoma Multiforme

Background: In 1997 MMAC1 or the PTEN gene, was identified as a tumor suppressor gene on the long arm of chromosome 10.PTEN involves in the balance between proliferation, and differentiation, apoptosis and regulation of angiogenesis, and eventually mutation in this gene causes a strong potential for tumorigenesis cells. This study is the first report of the correlation between PTEN gene mutations with histological markers and the age of Glioblastoma patients with the purpose of using it to remove diagnostic ambiguities and identify the type of glioma.

Methods: In this study, we screened for PTEN mutations in exon 4-8 in glioblastoma patients in Isfahanian population. Genomic DNA ware extract from 60 formalin fixed frozen glioblastoma tumors, 4 normal tissue sample and 60 blood samples. Mutational analysis was performed using polymerase chain reaction, single strand conformation polymorphism (SSCP) and heteroduplex mobility techniques. In order to augment the accuracy, the experiments (PCR, SSCP, HMA) was repeated at least 3 times. The correlation between PTEN mutations with Clinical Pathologic markers (pleomorphism, Necrosis, cellularity, mitosis and endothelial proliferation) in Glioblastoma tumors and the age of patients were investigated With the help of statistical tests (t-test, Manvitni and Fisher's exact test).

Results: A total of 4 mutations (7%) were detected in 60 glioblastoma tumors. In this study, there was no significant relation between clinic pathologic markers and PTEN mutations (p-value > 0.05). Our data shows a positive association between the age of onset of cancer and PTEN mutations (p-value < 0.001).

Conclusion: Our results suggested that PTEN mutations are Low in Iranian glioblastoma patients. People with PTEN mutations are more likely to develop glioblastoma before the age of 20.