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. Author manuscript; available in PMC: 2013 Apr 4.
Published in final edited form as: Nature. 2012 Sep 23;490(7418):61–70. doi: 10.1038/nature11412

Figure 3. Integrated analysis of the PI3K, TP53, and RB1 pathways.

Figure 3

Breast cancer subtypes differ by genetic and genomic targeting events, with corresponding effects on pathway activity. For a) PI3K, b) TP53 and c) RB1 pathways, key genes were selected using prior biological knowledge. Multiple mRNA expression signatures for a given pathway were defined (details in Supplemental Methods; PI3K:Saal, PTEN loss in human breast tumors; PI3K:CMap, PI3K/mTOR inhibitor treatment in vitro; PI3K:Majumder, Akt over-expression in mouse model; p53:IARC, expert-curated p53 targets; p53:GSK, TP53 mutant versus wild-type cell lines; p53:KANNAN, p53 over-expression in vitro; p53:TROESTER, TP53 knockdown in vitro; Rb:CHICAS, RB1 mouse knockout versus wild-type; Rb:LARA, RB1 knockdown in vitro; Rb:HERSCHKOWITZ, RB1 LOH in human breast tumors) and applied to the gene expression data, in order to score each tumor for relative signature activity (yellow: more active). The PI3K panel includes a protein-based (RPPA) proteomic signature. Tumors were ordered first by mRNA-subtype, though specific ordering differs between the panels. P-values were calculated by a Pearson’s correlation or a Chi-squared test.