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Systematic variation in gene expression patterns in human cancer cell lines

Nature Genetics volume 24, pages 227–235 (2000)Cite this article

Abstract

We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo.

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Figure 1: Gene expression patterns related to the tissue of origin of the cell lines.
Figure 2: Gene expression patterns related to other cell-line phenotypes.
Figure 3: Gene clusters related to tissue characteristics in the cell lines.
Figure 4: Comparison of the gene expression patterns in clinical breast cancer specimens and cultured breast cancer and leukaemia cell lines.
Figure 5: Histologic features of breast cancer biopsies can be recognized and parsed based on gene expression patterns.

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Acknowledgements

We thank members of the Brown and Botstein labs for helpful discussions. This work was supported by the Howard Hughes Medical Institute and a grant from the National Cancer Institute (CA 077097). The work of U.S. and J.N.W. was supported in part by a grant from the National Cancer Institute Breast Cancer Think Tank. D.T.R is a Walter and Idun Berry Fellow. M.B.E. is an Alfred P. Sloan Foundation Fellow in Computational Molecular Biology. C.M.P. is a SmithKline Beecham Pharmaceuticals Fellow of the Life Science Research Foundation. P.O.B. is an Associate Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Departments of Biochemistry, Stanford University School of Medicine, Stanford, California, USA

    Douglas T. Ross, Vishwanath Iyer & Patrick O. Brown

  2. Department of Genetics, Stanford University School of Medicine, Stanford, California, USA

    Michael B. Eisen, Charles M. Perou, Christian Rees, Paul Spellman, Alexander Pergamenschikov & David Botstein

  3. Department of Surgery, Stanford University School of Medicine, Stanford, California, USA

    Stefanie S. Jeffrey

  4. Department of Pathology, Stanford University School of Medicine, Stanford, California, USA

    Matt Van de Rijn

  5. Division of Basic Sciences, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

    Uwe Scherf, Mark Waltham & John N. Weinstein

  6. Incyte Pharmaceuticals, Fremont, California, USA

    Jeffrey C.F. Lee & Dari Shalon

  7. Genometrix Inc, The Woodlands, Texas, USA

    Deval Lashkari

  8. Division of Cancer Treatment and Diagnosis, Information Technology Branch, Developmental Therapeutics Program, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA

    Timothy G. Myers

  9. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA

    Patrick O. Brown

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  1. Douglas T. Ross
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Correspondence to John N. Weinstein or Patrick O. Brown.

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Ross, D., Scherf, U., Eisen, M. et al. Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet 24, 227–235 (2000). https://doi.org/10.1038/73432

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