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This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: ERC-09-0065v1 17/1/87    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Unger, K. Articles by Zitzelsberger, H. Search for Related Content PubMed PubMed Citation Articles by Unger, K. Articles by Zitzelsberger, H.

Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Department of Radiation Cytogenetics, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
¹ Department Biologie II, Anthropologie und Humangenetik, Ludwig Maximilians Universität, 82152 Martinsried, Germany
² Bute Medical School, University of St Andrews, St Andrews, Fife KY16 9TS Scotland, UK
³ Institut für Pathologie, Helmholtz Zentrum München – Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
⁴ Cambridge University Centre for Veterinary Science, University of Cambridge, Cambridge CB3 0ES, UK
⁵ Strahlenbiologisches Institut, Helmholtz Zentrum München – Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
⁶ Department of Molecular Cell Biology, Leiden University Medical Center, Einsteinweg 20, 2333 ZC Leiden, The Netherlands
⁷ Anatomia Patologica, Università di Bologna, Ospedale Bellaria, Via Altura 3, 40139 Bologna, Italy

(Correspondence should be addressed to H Zitzelsberger; Email: zitzelsberger{at}helmholtz-muenchen.de)

(K Unger is now at the Department of Histopathology, Imperial College London, London, UK)

Chromosomal copy number alterations and chromosomal rearrangements are frequent mutations in human cancer. Unlike copy number alterations, little is known about the role and occurrence of chromosomal rearrangements in breast cancer. This may be due to the fact that chromosome-based breakpoint analysis is widely restricted to cultured cells. In order to identify gene rearrangements in breast cancer, we studied the chromosomal breakpoints in radiation-transformed epithelial breast cell lines using a high-resolution array-based approach using 1 Mb bacterial artificial chromosome (BAC) arrays. The breakpoints were further narrowed down by fluorescence in situ hybridisation (FISH) with clones from the 32 k BAC library. The analysis of the cell lines B42-11 and B42-16 revealed rearrangements of chromosomes 7, 8, 10 and 12. We identified the genes Has2, Grid1, Ret, Cpm, Tbx3, Tbx5, Tuba1a, Wnt1 and Arf3 within the breakpoint regions. Quantitative RT-PCR showed a deregulated expression of all of these candidate genes except for Tbx5 and Tbx3. This is the first study demonstrating gene rearrangements and their deregulated mRNA expression in radiation-transformed breast cells. Since the gene rearrangements occurred in the transformed and tumourigenic cell lines only, it is likely that these were generated in conjunction with malignant transformation of the epithelial breast cells and therefore might reflect early molecular events in breast carcinogenesis. Initial studies indicate that these gene alterations are also found in sporadic breast cancers.