Analysis of PTEN/MMAC1 alteration in neuroblastoma

Neuroblastoma is the most common extracranial solid tumor in children. Alth ough it has been re ported that loss of heterozygosity at various loci, inc luding 10q, frequently occurs in neuroblastoma, a bona fide tumor suppresso r gene has not been identified. Recently, a gene mapped to chromosome 10q23 , PTEN/MMAC1, was identified as a tumor suppressor gene that inhibits cell survival and cell proliferation by catalyzing the dephosphorylation of phos phatidylinositol 3,4,5-triphosphate. To screen for mutations of this gene i n neuroblastoma, we analyzed 11 primary neuroblastoma tumors and 16 neurobl astoma cell lines for PTEN/MMAC1 mutations and deletions. All nine exons of the PTEN/MMAC1 gene were examined using the polymerase chain reaction-sing le strand conformational polymorphism assay and sequencing. Only one of the cell lines showed a mutation, a l-bp frameshift deletion in exon 7, and an allelic loss in the opposite allele was revealed by a microsatellite analy sis. Our results indicate that the disruption of the PTEN/MMAC1 gene is not a frequent event in neuroblastoma, and suggest that this disruption may be responsible for malignant progression in only a limited proportion of case s of neuroblastoma. (C) 2001 Elsevier Science Inc. All rights reserved.