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Genomewide assessment of genetic alterations in DMBA‐induced rat sarcomas: Cytogenetic, CGH, and allelotype analyses reveal recurrent DNA copy number changes in rat chromosomes 1, 2, 4, and 7
Author(s) -
Walentinsson Anna,
Sjöling Åsa,
Helou Khalil,
KlingaLevan Karin,
Levan Göran
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(200006)28:2<184::aid-gcc7>3.0.co;2-v
Subject(s) - biology , dmba , genetics , microsatellite , carcinogenesis , allele , chromosome , copy number variation , aneuploidy , microbiology and biotechnology , cancer research , gene , genome
Rat sarcomas, induced by subcutaneous injections of 7,12‐dimethylbenz[a]anthracene (DMBA), were studied with the objective of identifying critical chromosome regions associated with tumorigenesis. We employed three genomewide screening techniques—cytogenetics, CGH, and allelotyping—in 19 DMBA‐induced sarcomas in F1 (BN/Han x LE/Mol) rats. The most conspicuous finding in the 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 RNO19q (5/19), as well as the proximal part of RNO4 (8/19) and the distal part of RNO7 (7/19). Reduction in copy number was seen in RNO17 (2/19). For the allelotyping, we used 318 polymorphic microsatellite marker loci covering the entire genome. We identified regions of allelic imbalance affecting most of the rat chromosomes. The highest incidences of recurrent allelic imbalance 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 suggested that genetic alterations detected in RNO2 and RNO12 usually corresponded to complete or partial trisomy, whereas those in RNO1 and RNO7 seemed to involve regional deletions and/or gains. Furthermore, we could confirm that copy number gains occur proximally in RNO4, where a previous study showed amplification of the Met oncogene in a subset of these tumors. Genes Chromosomes Cancer 28:184–195, 2000. © 2000 Wiley‐Liss, Inc.