MUTATION ANALYSIS AND LOSS OF HETEROZYGOSITY OF PEDF IN CENTRAL-NERVOUS-SYSTEM PRIMITIVE NEUROECTODERMAL TUMORS

Deletion of 17p is the most frequent abnormality observed in central n ervous system (CNS) primitive neuroectodermal tumors (PNETs), implicat ing the presence of a tumor suppressor gene which maps to 17p. The gen e for pigment epithelium-derived factor (PEDF) has been cloned and map ped to 17p13. PEDF belongs to the serine protease inhibitor (SERPIN) g ene family. The PEDF protein has neurotrophic and neuronal-survival ac tivities and is expressed in the CNS. Twenty tumor and matched normal DNA samples from patients with PNETs were screened by single-strand co nformation polymorphism (SSCP) analysis to determine loss of heterozyg osity (LOH) and to identify potential mutations within the 8 exons of the PEDF gene. Ten of the 20 tumors demonstrated LOH, consistent with the deletion status of 17p determined by cytogenetic or fluorescence i n site hybridization studies. SSCP analysis of the genomic DNA from th e IO cases with LOH demonstrated several polymorphisms in exons 4 and 7, but no mutations. Our results are consistent with a loss of alleles on 17p in 50% of CNS PNETs, but do not suggest that PEDF is a candida te for the PNET suppressor gene in 17p 13. (C) 1997 Wiley-Liss, Inc.