Nature Genetics
24, 227 - 235 (2000)
doi:10.1038/73432
Systematic variation in gene expression patterns in human cancer cell
linesDouglas T. Ross1, Uwe Scherf5, Michael B. Eisen2, Charles M. Perou2, Christian Rees2, Paul Spellman2, Vishwanath Iyer1, Stefanie S. Jeffrey3, Matt Van de Rijn4, Mark Waltham5, Alexander Pergamenschikov2, Jeffrey C.F. Lee6, Deval Lashkari7, Dari Shalon6, Timothy G. Myers8, John N. Weinstein5, David Botstein2
& Patrick O. Brown1, 91
Departments of Biochemistry, Stanford University School
of Medicine, Stanford, California, USA.
2
Department of Genetics, Stanford University School
of Medicine, Stanford, California, USA.
3
Department of Surgery, Stanford University School of
Medicine, Stanford, California, USA.
4
Department of Pathology, Stanford University School
of Medicine, Stanford, California, USA.
5
Laboratory of Molecular Pharmacology, Division of Basic
Sciences, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, USA. 6
Incyte Pharmaceuticals, Fremont,
California, USA. 7
Genometrix Inc., The Woodlands,
Texas, USA. 8
Information Technology Branch, Developmental Therapeutics
Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute,
National Institutes of Health, Rockville, Maryland,
USA. 9
Howard Hughes Medical Institute, Stanford University
School of Medicine, Stanford, California,
USA.
Correspondence should be addressed to Patrick O. Brown pbrown@cmgm.stanford.edu or John N. Weinstein Weinstein@dtpax2.ncifcrf.gov.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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