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Repeated observation of breast tumor subtypes in independent gene expression data sets
Departments of *Genetics,
Health, Research and Policy, and Statistics,
Statistics and Health, and
Biochemistry and Howard Hughes Medical
Institute, Stanford University School of Medicine, Stanford, CA 94305;
Departments of Genetics and
Pathology and Laboratory Medicine,
Lineberger Comprehensive Cancer Center, and Departments of
¶Statistics and
||Biostatistics, University of North Carolina,
Chapel Hill, NC 27599; Department of
Medicine, Section of Oncology, Haukeland University Hospital, 5021 Bergen,
Norway; and **Department of Genetics, Norwegian
Radium Hospital, 0310 Oslo, Norway
Contributed by David Botstein, May 5, 2003
Characteristic patterns of gene expression measured by DNA microarrays have been used to classify tumors into clinically relevant subgroups. In this study, we have refined the previously defined subtypes of breast tumors that could be distinguished by their distinct patterns of gene expression. A total of 115 malignant breast tumors were analyzed by hierarchical clustering based on patterns of expression of 534 "intrinsic" genes and shown to subdivide into one basal-like, one ERBB2-overexpressing, two luminal-like, and one normal breast tissue-like subgroup. The genes used for classification were selected based on their similar expression levels between pairs of consecutive samples taken from the same tumor separated by 15 weeks of neoadjuvant treatment. Similar cluster analyses of two published, independent data sets representing different patient cohorts from different laboratories, uncovered some of the same breast cancer subtypes. In the one data set that included information on time to development of distant metastasis, subtypes were associated with significant differences in this clinical feature. By including a group of tumors from BRCA1 carriers in the analysis, we found that this genotype predisposes to the basal tumor subtype. Our results strongly support the idea that many of these breast tumor subtypes represent biologically distinct disease entities.
¶¶ To whom correspondence should be addressed. E-mail: botstein{at}genome.stanford.edu.
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