Cytogenetic aberrations in spontaneous endometrial adenocarcinomas in the BDII rat model as revealed by chromosome banding and comparative genome hybridization.
Female rats of the inbred strain BDII are genetically predisposed to endometrial estrogen-dependent adenocarcinomas (EAC). More than 90% of them spontaneously develop this tumor type before the age of 24 months. In order to dissect out the genetic components behind these tumors we have made crosses between BDII females and rats from 2 other strains that are nonsusceptible to EAC. It was found that EAC tumors developed in a subset of intercross and backcross animals from both interstrain crosses. The chromosomal changes in the developing tumors were studied using cytogenetic and molecular cytogenetic methods. From these studies, we conclude that certain chromosome regions were recurrently engaged in chromosomal changes such as increases in copy number (e.g., trisomy, amplification) or decreases (e.g., deletion). Based on the analysis of 56 tumors, 8 regions were found to be particularly often involved: RNO4prx, gain=34 (61%) (amplification 12 cases); RNO5mid, loss=15 (27%); RNO6prx, gain=25 (45%) (amplification 8 cases); RNO10 loss, prx-mid/gain dst=25 (45%) (amplification 1 case); RNO12q, gain=23 (41%); RNO15p loss/RNO15q gain=29 (52%) (amplification 1 case) [RNO, rat chromosome; prx, proximal; mid, middle; dst, distal; p, short arm; q, long arm]. We begun to analyze these regions in detail using various molecular methods and within them there are certain possible target genes, such as MET (RNO4q21), CDKN2A/2B (RNO5q32), MYCN (RNO6q15 approximately q16), and TP53 (RNO10q24 approximately q25), but it is clear that several other genes, still unidentified, must also be involved.
Hamta
Ahmad
A
CMB-Genetics, Lundberg Laboratory, Göteborg University, Box 462, SE 40530, Gothenburg, Sweden.
Adamovic
Tatjana
T
Heloua
Khalil
K
Levan
Göran
G
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D003433:Crosses, Genetic; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains