Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis.
Loss of heterozygosity for sequences located on chromosome 17p in several tumor types is often associated with mutations in the tumor suppressor gene p53. We previously showed consistent deletion of chromosome 17p12-13.1 in medulloblastoma, a common childhood brain tumor. Using denaturing gradient gel electrophoresis and direct sequencing, we have detected p53 mutations in only two of 20 medulloblastoma specimens. Moreover, additional RFLP studies of these 20 specimens showed loss of heterozygosity at a more distal and distinct site, 17p13.3. Deletion of 17p almost invariably signified a negative prognosis. Our results suggest that p53 mutations may contribute to the pathogenesis of medulloblastoma in relatively few cases. The consistent deletion of other discrete loci on 17p suggests that additional or alternative tumor suppressor genes may contribute to the tumor's phenotype.
Department of Neurological Surgery, School of Medicine, University of California, San Francisco.
P H
PH
Cogen
L
L
Daneshvar
A K
AK
Metzger
G
G
Duyk
M S
MS
Edwards
V C
VC
Sheffield
D001483:Base Sequence; D002528:Cerebellar Neoplasms / Q000209:etiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D016521:Electrophoresis, Gel, Pulsed-Field; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008527:Medulloblastoma / Q000209:etiology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis