Loss of constitutional heterozygosity in human astrocytomas.
Inactivation of tumour suppressor genes or anti-oncogenes as well as activation of dominant acting oncogenes seem to be important mechanisms in the pathogenesis of gliomas. We compared constitutional and tumoural genotypes at different restriction fragment length polymorphism loci (RFLP) on chromosomes 10 and 17 in 15 unrelated individuals. Loss of heterozygosity (LOH) pointing to chromosomal loss or deletions was detected for at least one chromosome 17 marker in 11 gliomas (astrocytomas grades I-III and glioblastoma multiforme), whereas LOH for chromosome 10 loci was only detected in 3 out of 9 cases of glioblastoma multiforme and was not detected in low grade gliomas. Since LOH for chromosome 10 loci seems to be restricted only to glioblastoma multiforme, it is possible that recessive mutations on chromosome 10 are engaged in tumour progression from astrocytomas to glioblastoma multiforme. As LOH of chromosome 17 markers occurs in astrocytomas as in glioblastoma multiforme, chromosome 17 loci probably are involved in early tumour development.
Van de Kelft
E
E
Department of Neurosurgery, Universitair Ziekenhuis Antwerpen, Belgium.
De Boulle
K
K
Willems
P
P
Martin
J J
JJ
Selosse
P
P
Van der Auwera
B
B
D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015139:Blotting, Southern; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics; D002879:Chromosomes, Human, Pair 10; D002886:Chromosomes, Human, Pair 17; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length
D015342:DNA Probes; D004273:DNA, Neoplasm; D005819:Genetic Markers