The retinoblastoma gene is involved in malignant progression of astrocytomas
- 1 November 1994
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 36 (5), 714-721
- https://doi.org/10.1002/ana.410360505
Abstract
Loss of chromosome 13q occurs in up to 50% of human astrocytomas, suggesting the presence of an astrocytoma tumor suppressor gene on that chromosome. To determine whether the retinoblastoma susceptibility gene (Rb) on 13q 14 contributes to the formation of astrocytomas, we examined 85 tumors for loss of heterozygosity (LOH) at the intragenic Rb 1.20 locus. LOH was detercted in 16 of 54 informative high‐grade astrocytomas (30%), but was not detected in 12 low‐grade gliomas. Deletion mapping with flanking markers on 13q revealed that the Rb 1.20 region was preferentially targeted by the deletions. Tumors with LOH at Rb 1.20 were examined for mutations in the remaining Rb allele using single‐strand conformational polymorphism (SSCP) analysis and direct DNA sequencing. Mutations were detected in exon 8 (1 tumor), exon 24 (2 tumors), and intron 24 (1 tumor). Rb protein expression, as assessed by immunohistochemistry, was altered in 3 of 9 cases with LOH and in 1 tumor without LOH. Our results demonstrate that Rb inactivation contributes to the formation of high‐grade astrocytomas, and therefore implicate a second, known tumor suppressor gene in astrocytoma tumorigenesis.Keywords
This publication has 21 references indexed in Scilit:
- Dilemmas and progress in mutation detectionTrends in Genetics, 1993
- A rapid and non‐radioactive PCR based assay for the detection of allelic loss in human gliomasNeuropathology and Applied Neurobiology, 1993
- THE TUMOR SUPPRESSOR GENESAnnual Review of Biochemistry, 1993
- Molecular characterization of the retinoblastoma susceptibility geneBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1993
- Subsets of Glioblastoma Multiforme Defined by Molecular Genetic AnalysisBrain Pathology, 1993
- Dinucleotide repeat polymorphisms at the D13S192 and D13S193 lociHuman Molecular Genetics, 1993
- Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomasGenes, Chromosomes and Cancer, 1992
- Molecular Genetics in the Pathology and Diagnosis of RetinoblastomaBrain Pathology, 1990
- A genetic model for colorectal tumorigenesisCell, 1990
- A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcomaNature, 1986