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Abstract

Human breast tumours are diverse in their natural history and in their responsiveness to treatments1. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.

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Acknowledgements

We thank W. Gerald and L. Norton for the three New York tumour specimens; M. Stampfer and P. Yaswen for the 184 sample mRNAs; and members of the P. O. Brown, D. Botstein and A.-L. Børresen-Dale labs for discussions. We are grateful to the NCI and the Howard Hughes Medical Institute who provided support for this research. C.M.P. is a SmithKline Beecham Pharmaceuticals Fellow of the Life Sciences Research Foundation. T.S. is a research fellow of the Norwegian Cancer Society. M.B.E. is an Alfred P. Sloan Foundation Postdoctoral Fellow in Computational Molecular Biology. D.T.R. is a Walter and Idun Berry Fellow. P.O.B. is an Associate Investigator of the Howard Hughes Medical Institute.

Author information

Author notes

    • Charles M. Perou
    •  & Therese Sørlie

    These authors contributed equally to this work

Affiliations

  1. *Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA

    • Charles M. Perou
    • , Michael B. Eisen
    • , Christian A. Rees
    • , Alexander Pergamenschikov
    • , Cheryl Williams
    •  & David Botstein
  2. ‡Department of Genetics, The Norwegian Radium Hospital, N-0310 Montebello Oslo, Norway

    • Therese Sørlie
    • , Hilde Johnsen
    •  & Anne-Lise Børresen-Dale
  3. §Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA

    • Matt van de Rijn
    •  & Shirley X. Zhu
  4. Department of Surgery, Stanford University School of Medicine, Stanford, California 94305 , USA

    • Stefanie S. Jeffrey
  5. ¶Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA

    • Jonathan R. Pollack
    • , Douglas T. Ross
    •  & Patrick O. Brown
  6. #Department of Pathology, The Gade Institute, Haukeland University Hospital, N-5021 Bergen, Norway

    • Lars A. Akslen
  7. Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway

    • Øystein Fluge
  8. **Department of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway

    • Per E. Lønning
  9. ††Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA

    • Patrick O. Brown

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https://doi.org/10.1038/35021093

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