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Target Discovery and Validation Reviews and Protocols

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106 Sørlie<br />

Fig. 5. Cluster of genes associated with TP53 mutational status. Hierarchical clustering<br />

of 158 genes whose expression levels were significantly correlated to the mutation<br />

status of the TP53 gene (SAM, false discovery rate < 1). Only tumor tissues from the<br />

two prospective studies from Norway were included in the cluster analysis. The tumor<br />

samples are ordered according to the clustering groups from Fig. 3. Frequencies of<br />

TP53 mutations are listed. Adapted from ref. 67.<br />

rate of less than 1% (67). The genes were clustered, whereas the samples were<br />

ordered according to the subtypes (Fig. 5). As expected, many of the genes that<br />

were highly expressed in the mutated tumors (mostly basal-like <strong>and</strong> luminal B<br />

type tumors) are cell cycle regulated genes such as PLK1, CCNA2, STK6, <strong>and</strong><br />

MAPK13 (17). Two of the genes coexpressed with ERBB2 oncogene, GRB7 <strong>and</strong><br />

STARD3, also were found in this gene list, but not the ERBB2 gene itself.<br />

Interestingly, many of the genes whose high expression <strong>and</strong> specific pattern

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