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Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model

Oncogene volume 24, pages 6101–6107 (2005)Cite this article

Abstract

Microarray-based formats offer a high-resolution alternative to conventional, chromosome-based comparative genomic hybridization (CGH) methods for assessing DNA copy number alteration (CNA) genome-wide in human cancer. For murine tumors, array CGH should provide even greater advantage, since murine chromosomes are more difficult to individually discern. We report here the adaptation and evaluation of a cDNA microarray-based CGH method for the routine characterization of CNAs in murine tumors, using mouse cDNA microarrays representing ∼14 000 different genes, thereby providing an average mapping resolution of 109 kb. As a first application, we have characterized CNAs in a set of 10 primary and recurrent lymphomas derived from a Myc-induced murine lymphoma model. In primary lymphomas and more commonly in Myc-independent relapses, we identified a recurrent genomic DNA loss at chromosome 3G3–3H4, and recurrent amplifications at chromosome 3F2.1–3G3 and chromosome 15E1/E2–15F3, the boundaries of which we defined with high resolution. Further, by profiling gene expression using the same microarray platform, we identified within CNAs the relevant subset of candidate cancer genes displaying comparably altered expression, including Mcl1 (myeloid cell leukemia sequence 1), a highly expressed antiapoptotic gene residing within the chr 3 amplicon peak. CGH on mouse cDNA microarrays therefore represents a reliable method for the high-resolution characterization of CNAs in murine tumors, and a powerful approach for elucidating the molecular events in tumor development and progression in murine models.

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Abbreviations

CGH:

comparative genomic hybridization

CNA:

copy number alteration

TSG:

tumor suppressor gene

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Acknowledgements

We are indebted to Mike Fero and the staff of the Stanford Functional Genomic Facility (SFGF) for providing high-quality cDNA microarrays, and to Gavin Sherlock and the staff of the Stanford Microarray Database (SMD) group for providing outstanding database support. We also thank Siegfried Janz who kindly provided us with the lymphoma cell line P388D1, and the RIKEN Genomic Sciences Center for providing microarray cDNA clones. L Bullinger was supported in part by the Deutsche Forschungsgemeinschaft, Bonn, Germany (Forschungsstipendium BU 1339/1), and J Pollack was supported in part by NIH Grant CA97139.

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Author notes

  1. Sandrine Sander and Lars Bullinger: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Pathology, Stanford University, Stanford, CA, USA

    Sandrine Sander, Lars Bullinger & Jonathan R Pollack

  2. Department of Medicine-Oncology, Stanford University, Stanford, CA, USA

    Asa Karlsson, Sylvie Giuriato & Dean W Felsher

  3. Department of Biochemistry, Stanford University, Stanford, CA, USA

    Tina Hernandez-Boussard

  4. Department of Internal Medicine III, University of Ulm, Ulm, Germany

    Sandrine Sander & Lars Bullinger

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  1. Sandrine Sander
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Correspondence to Jonathan R Pollack.

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Sander, S., Bullinger, L., Karlsson, A. et al. Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model. Oncogene 24, 6101–6107 (2005). https://doi.org/10.1038/sj.onc.1208751

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