PEDIATRIC BRAIN-TUMORS - LOSS OF HETEROZYGOSITY AT 17P AND TP53 GENE-MUTATIONS

Cytogenetic and molecular analyses of primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) have demonstrated materia l losses of 17p, the region that contains the TP53 gene, as the most f requent abnormality. Mutations in the TP53 gene are, however, very rar e in these tumors. These findings strongly suggest that another, as ye t unidentified, gene on 17p may be involved. We performed a search for loss of heterozygosity (LOH) on 17p by microsatellite markers on 26 c hildhood CNS tumors as well as TP53 gene mutations (exons 5-8) by sing le-strand conformational polymorphism analysis on 41 pediatric brain t umor samples of distinct histologic types. LOH was detected in 10 case s: 7 PNET, 2 astrocytomas, and 1 glioblastoma mutliforme. In 4 of the PNETs the losses were limited to more distal markers. On the other han d, TP53 mutations were detected in 6 of 41 samples studied. Our result s not only confirm the low penetrance of the TP53 gene on pediatric CN S tumors, but also provide further evidence of a putative tumor suppre ssor gene distal to TP53, between markers (D17S938, D17S926) and 17pte r, specifically taking part in the development of PNET. (C) Elsevier S cience Inc., 1998.