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BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
Sahlgrenska Academy, University of Gothenburg.
Sahlgrenska Academy, University of Gothenburg.
University of Gothenburg.
Chalmers University of Technology.
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2012 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, artikelnummer 352- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central, 2012. Vol. 12, artikelnummer 352- p.
National Category
Biological Sciences
Research subject
Natural sciences
Identifiers
URN: urn:nbn:se:his:diva-6545DOI: 10.1186/1471-2407-12-352ISI: 000310632100001PubMedID: 22894538Scopus ID: 2-s2.0-84864931479OAI: oai:DiVA.org:his-6545DiVA: diva2:561145
Available from: 2012-10-17 Created: 2012-10-17 Last updated: 2017-12-07

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