BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors.
BACKGROUND
Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis.


METHODS
Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene) in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding) and Comparative Genome Hybridization (CGH) analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome) CGH-array platform.


RESULTS
Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO) band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors.


CONCLUSIONS
Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve genes with a critical role in mammary tumor development. Genetic changes identified in this work are at very small scales and thus may provide a more feasible basis for the identification of the target gene(s). Identification of the genes underlying these chromosome changes can provide new insights to the mechanisms of mammary carcinogenesis.
Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-40530, Göteborg, Sweden.
Emma
E
Samuelson
Sara
S
Karlsson
Karolina
K
Partheen
Staffan
S
Nilsson
Claude
C
Szpirer
Afrouz
A
Behboudi
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D022202:Chromosomes, Artificial, Bacterial; D033481:Chromosomes, Mammalian; D055028:Comparative Genomic Hybridization; D004171:Diploidy; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D051381:Rats; D011921:Rats, Inbred WKY
D015127:9,10-Dimethyl-1,2-benzanthracene