Molecular portraits of human breast tumours

Human breast tumours are diverse in their natural history and in their resp onsiveness to treatments(1). Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each c ell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the le vel of expression of every gene in the genome. Here we have characterized v ariation in gene expression patterns in a set of 65 surgical specimens of h uman breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a disti nctive molecular portrait of each tumour. Twenty of the tumours were sample d twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient . Gene expression patterns in two tumour samples from the same individual w ere almost always more similar to each other than either was to any other s ample. Sets of co-expressed genes were identified for which variation in me ssenger RNA levels could be related to specific features of physiological v ariation. The tumours could be classified into subtypes distinguished by pe rvasive differences in their gene expression patterns.