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Clonal genomic alterations in glioma malignancy stages
C D James1, E Carlbom, J P Dumanski
1Ludwig Institute for Cancer Research, Montreal, Canada.
Cancer Research
|October 1, 1988
Summary
Loss of chromosome 10 sequences is strongly linked to glioblastoma, the most aggressive form of glioma. This genetic change suggests glioblastoma develops from earlier tumor stages via a common molecular pathway.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Recessive mutations predispose to cancer.
- Genomic analysis of tumor genotypes aids in understanding cancer development.
Purpose of the Study:
- To investigate genetic alterations in glial tumors.
- To determine the association between specific chromosomal losses and glioma malignancy grade.
Main Methods:
- Comparative genomic hybridization (CGH) was used.
- Restriction fragment length polymorphism (RFLP) analysis was performed on tumor and constitutional DNA from 53 patients.
- Tumor genotypes were compared to constitutional genotypes at specific chromosomal loci.
Main Results:
- Loss of heterozygosity (LOH) on chromosome 10 was found in 28/29 glioblastoma (grade IV) tumors.
- No LOH on chromosome 10 was observed in 22 lower-grade gliomas.
- Nonrandom LOH on chromosomes 13, 17, and 22 occurred across various glioma grades.
Conclusions:
- Loss of chromosome 10 sequences is closely associated with glioblastoma.
- Glioblastoma likely arises from clonal expansion of precursor cells through a common molecular pathway.
- Somatic LOH analysis offers a genotypic approach to studying tumor progression.