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Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis

Oncogene volume 28, pages 1892–1903 (2009)Cite this article

Abstract

Co-amplification at chromosomes 8p11–8p12 and 11q12–11q14 occurs often in breast tumors, suggesting possible cooperation between genes in these regions in oncogenesis. We used high-resolution array comparative genomic hybridization (array CGH) to map the minimal amplified regions. The 8p and 11q amplicons are complex and consist of at least four amplicon cores at each site. Candidate oncogenes mapping to these regions were identified by combining copy number and RNA and protein expression analyses. These studies also suggested that CCND1 at 11q13 induced expression of ZNF703 mapping at 8p12, which was subsequently shown to be mediated by the Rb/E2F pathway. Nine candidate oncogenes from 8p12 and four from 11q13 were further evaluated for oncogenic function. None of the genes individually promoted colony formation in soft agar or collaborated with each other functionally. On the other hand, FGFR1 and DDHD2 at 8p12 cooperated functionally with MYC, whereas CCND1 and ZNF703 cooperated with a dominant negative form of TP53. These observations highlight the complexity and functional consequences of the genomic rearrangements that occur in these breast cancer amplicons, including transcriptional cross-talk between genes in the 8p and 11q amplicons, as well as their cooperation with major pathways of tumorigenesis.

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Acknowledgements

We thank members of the UCSF Helen Diller Family Comprehensive Cancer Center Genome Analysis, Informatics, and Microarray Shared Resources for performing the TaqMan assays and printing the custom 8p11q array. This work was supported by NIH Grants CA90421 and CA101359. Serena S Kwek was the recipient of a DOD BCRP fellowship, Grant nos. BC021074, DAMD17-03-1-0483.

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Author notes

  1. S S Kwek

    Present address: 7Current address: Department of Hematology/Oncology, University of California San Francisco, San Francisco, CA 94143, USA,

  2. H Zhou

    Present address: 8Current address: Epitomics, 863 Mitten Road, Suite 103, Burlingame, CA 94010, USA,

  3. J Fridlyand

    Present address: 9Current address: Department of Early Clinical Development Statistics, Genentech Inc., South San Francisco, CA, USA,

Authors and Affiliations

  1. Cancer Research Institute, University of California San Francisco, San Francisco, CA, USA

    S S Kwek, H Zhou, J Climent & D G Albertson

  2. University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA

    R Roy, J Fridlyand & D G Albertson

  3. Department of Hematology and Medical Oncology, Hospital Clinico, Valencia, Spain

    J Climent

  4. Division of Oncology, Center for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain

    J A Martinez-Climent

  5. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA

    J Fridlyand

  6. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA

    D G Albertson

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Correspondence to D G Albertson.

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Kwek, S., Roy, R., Zhou, H. et al. Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis. Oncogene 28, 1892–1903 (2009). https://doi.org/10.1038/onc.2009.34

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