Incidence of p14ARF gene deletion in high-grade adult and pediatric astrocytomas

摘要: The INK4a-ARF locus encodes 2 separate proteins through differential splicing of alternative first exons to produce p16 INK4a (exon 1α) and p14 ARF 1β) products in human cells. protein inhibits the cyclin D-dependent kinases (CDK) that control phosphorylation Rb cell proliferation. gene product can complex with sequester MDM2 within nucleus, thus modulating activity p53 protein. Loss expression would disrupt retinoblastoma (Rb)/p16 /cyclin kinase (CDK4) pathway, whereas loss inactivate both p53/MDM2/p14ARF pathways MDM2, which either or p53. on 9p21 has been documented a wide range tumors, including one third glioblastomas. However, tumors showing homozygous exon gene, 1β not established. In this study, we have assessed deletion 29 pediatric 107 adult high-grade astrocytomas 9 glioma lines, using multiplex PCR analysis for 1β. We found deletions 1α 3 (10%) cases (2 grade III, 1 IV), 25 (23%) (6 III 19 8 (89%) lines. Therefore, may contribute highly malignant behavior treatment resistance these elimination multiple checkpoint cycle proteins.