Published in Nature Genetics, vol. 24, no. 3, pp. 227-235 (March, 2000):


"Systematic Variation in Gene Expression Patterns in Human Cancer Cell Lines."

Douglas T. Ross 1, Uwe Scherf 5, Michael B. Eisen 2, Charles M. Perou 2 , Christian Rees 2 , Paul Spellman 2 , Vishwanath Iyer 1 , Stefanie S. Jeffrey 3 , Matt Van de Rijn 4 , Mark Waltham 5 , Alexander Pergamenschikov 2 , Jeffrey C.F. Lee 6 , Deval Lashkari 7 , Dari Shalon 6 , Timothy G. Myers 8 , John N. Weinstein 5 , David Botstein 2 and Patrick O. Brown 1, 9.


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.

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.



Additional References:

1. Neiman PE, and Henry PH, "RNA-DNA Hybridization and Hybridization-Competition Studies of the Rapidly-Labeled RNA from Normal and Chronic Lymphocytic Leukemia Lymphocytes", Biochemistry 8: 275-282 (1969).

2. Turkington RW, "Changes in Hybridizable RNA during the Neoplastic Development of Mouse Mammary Cells", Cancer Res. 31: 427-432 (1971).


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