Repeated observation of breast tumor subtypes in independent gene expression data sets

Proceedings of the National Academy of Sciences of the United States of America - Tập 100 Số 14 - Trang 8418-8423 - 2003
Thérese Sørlie1, Robert Tibshirani1,2, Joel S. Parker1, Trevor Hastie1, J. S. Marron1, Andrew B. Nobel1, Shibing Deng1, Hilde Johnsen1, Robert Pesich1, Stephanie Geisler1,2, János Demeter3,1,2, Charles M. Perou1, Per Eystein Lønning1,2, Patrick O. Brown1,2,4, Anne‐Lise Børresen‐Dale1, David Botstein1
1Departments 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...
2Health, Research and Policy, and Statistics,
3Department of Genetics, Norwegian Radium Hospital, 0310 Oslo, Norway
4Statistics and Health, and

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 100 Số 14

8418-8423

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