Allele-specific losses of heterozygosity on chromosomes 1 and 17 revealed by whole genome scan of ethylnitrosourea-induced BDIX x BDIV hybrid rat gliomas.
The induction of neural tumors by N-ethyl-N-nitrosourea (EtNU) in inbred strains of rats has evolved as a valuable model system of developmental stage- and cell type-dependent oncogenesis. Tumor yield and latency times are strongly influenced by genetic background. Compared with BDIX rats, BDIV rats are relatively resistant to the induction of brain tumors by EtNU, with a lower tumor incidence and latency periods prolonged by a factor of 3. To characterize genetic abnormalities associated with impaired tumor suppressor gene function in neuro-oncogenesis, losses of heterozygosity (LOHs) and microsatellite instability (MI) were investigated in brain tumors induced by EtNU in (BDIV x BDIX) F(1) and F(2) rats. The polymerase chain reaction was used to amplify 55 polymorphic microsatellite markers spanning the entire rat genome. The tumors displayed different histologies and grades of malignancy, corresponding to part of the spectrum of human gliomas. MI was not observed in any of the tumors. LOH of rat chromosome 1q was predominantly detected in oligodendrogliomas and mixed gliomas, with a 30% incidence in informative cases. 11p15.5, the human genome region syntenic to the consensus region of LOHs observed on rat chromosome 1, has been shown to be involved in the formation of gliomas in humans. Furthermore, rat brain tumors of different histologies often showed allelic imbalances on chromosome 17p. In both cases of LOH, there was a clear bias in favor of the parental BDIV allele, suggesting the involvement of tumor suppressor genes functionally polymorphic between the two rat strains.
Kindler-Röhrborn
A
A
Institute of Cell Biology (Cancer Research), University of Essen Medical School and West German Cancer Center Essen, Essen, Germany.
Koelsch
B U
BU
Buslei
R
R
Zabel
S
S
Wiestler
O D
OD
Rajewsky
M F
MF
D000483:Alleles; D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D002678:Chimera / Q000187:drug effects / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes / Q000187:drug effects* / Q000235:genetics; D005038:Ethylnitrosourea / Q000494:pharmacology*; D008040:Genetic Linkage; D005819:Genetic Markers; D005910:Glioma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D005819:Genetic Markers; D005038:Ethylnitrosourea