Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indices.

摘要: p16 is involved in a cell-cycle regulatory cascade that includes cyclin-dependent kinase 4 (cdk4), cyclin D1 and pRb. Alterations of each these components have been described primary human glioblastoma multiforme (GBM) or GBM cell lines, alterations the individual this pathway appear inversely correlated with one another. While suggests disruption any component has similar oncogenic effects, homozygous deletions CDKN2/p16 gene are most common genetic alteration. We investigated relationship between cellular proliferation 50 astrocytomas (2 WHO grade I pilocytic astrocytoma, 15 II astrocytomas, 20 III anaplastic 13 IV GBMs). Using comparative multiplex PCR assay, were detected 5 (25%) 6 GBMs (46%), but none lower-grade tumors. Ki-67 immunohistochemistry was used to assess number proliferating cells same samples for molecular analysis. In both GBMs, indices significantly higher tumors (20%) than those without (10%; p=0.0001). These results suggest high-grade may more deleterious effect on cycle control other aberrations p16-cdk4-cyclin D1-pRb pathway, provide explanation why events RB mutations CDK4 amplification.