Human breast tumours are diverse in their natural history and in
their responsiveness to treatments1. Variation in transcriptional
programs accounts for much of the biological diversity of human
cells and tumours. In each cell, signal transduction and regulatory
systems transduce information from the cell's identity to its
environmental status, thereby controlling the level of expression
of every gene in the genome. Here we have characterized variation
in gene expression patterns in a set of 65 surgical specimens of
human breast tumours from 42 different individuals, using
complementary DNA microarrays representing 8,102 human
genes. These patterns provided a distinctive molecular portrait
of each tumour. Twenty of the tumours were sampled 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 were almost always more
similar to each other than either was to any other sample. Sets
of co-expressed genes were identi®ed for which variation in
messenger RNA levels could be related to speci®c features of
physiological variation. The tumours could be classi®ed into
subtypes distinguished by pervasive differences in their gene
expression patterns.