Systematic Variation in Gene Expression Patterns
in Human Cancer Cell Lines
Douglas 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 9
1. 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 P O Brown. e-mail:
pbrown@cmgm.stanford.edu
and J N Weinstein. e-mail:
Weinstein@dtpax2.ncifcrf.gov.
Nature Genetics, 24(3), 227-235 (2000)
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