Genomewide assessment of genetic alterations in DMBA-induced rat sarcomas:Cytogenetic, CGH, and allelotype analyses reveal recurrent DNA copy numberchanges in rat chromosomes 1, 2, 4, and 7
A. Walentinsson et al., Genomewide assessment of genetic alterations in DMBA-induced rat sarcomas:Cytogenetic, CGH, and allelotype analyses reveal recurrent DNA copy numberchanges in rat chromosomes 1, 2, 4, and 7, GENE CHROM, 28(2), 2000, pp. 184-195
Rat sarcomas, induced by subcutaneous injections of 7,12-dimethylbenz[a]ant
hracene (DMBA), were studied with the objective of identifying critical chr
omosome regions associated with tumorigenesis. We employed three genomewide
screening techniques-cytogenetics, CGH, and allelotyping-in 19 DMBA-induce
d sarcomas in FI (BN/Han x LE/Mol) rats. The most conspicuous finding in th
e cytogenetic analysis was a high incidence of trisomy for rat chromosome 2
(RNO2). Signs of gene amplification (hsr) were also seen in several tumors
. The CGH analysis revealed that gains in copy number were much more common
than losses. The gains mostly affected RNO2 (10/19), RNO12q (7/19), and RN
O19q (5/19), as well as the proximal part of RNO4 (8/19) and the distal par
t of RNO7 (7/19). Reduction in copy number was seen in RNO17 (2/19). For th
e allelotyping, we used 318 polymorphic microsatellite marker loci covering
the entire genome. We identified regions of allelic imbalance affecting mo
st of the rat chromosomes. The highest incidences of recurrent allelic imba
lance were observed at loci in certain regions in RNO1, 2, 4, and 7 and at
lower incidences in parts of RNO12, 16, 18, and 19. The combined results su
ggested that genetic alterations detected in RNO2 and RNO12 usually corresp
onded to complete or partial trisomy, whereas those in RNO1 and RNO7 seemed
to involve regional deletions and/or gains. Furthermore, we could confirm
that co-py number gains occur proximally in RNO4, where a previous study sh
owed amplification of the Met oncogene in a subset of these tumors. Genes C
hromosomes Cancer 28: 184-195, 2000. (C) 2000 Wiley-Liss, Inc.