Figure 3: Integrated analysis of the PI(3)K, TP53 and RB1 pathways. | Nature

Figure 3: Integrated analysis of the PI(3)K, TP53 and RB1 pathways.

From: Comprehensive molecular portraits of human breast tumours

Figure 3

Breast cancer subtypes differ by genetic and genomic targeting events, with corresponding effects on pathway activity. ac, For PI(3)K (a), TP53 (b) and RB1 (c) pathways, key genes were selected using prior biological knowledge. Multiple mRNA expression signatures for a given pathway were defined (details in Supplementary Methods; PI(3)K:Saal, PTEN loss in human breast tumours; CMap, PI(3)K/mTOR inhibitor treatment in vitro; Majumder, Akt overexpression in mouse model; TP53: IARC, expert-curated p53 targets; GSK, TP53 mutant versus wild-type cell lines; KANNAN, TP53 overexpression in vitro; TROESTER, TP53 knockdown in vitro; RB: CHICAS, RB1 mouse knockout versus wild type; LARA, RB1 knockdown in vitro; HERSCHKOWITZ, RB1 loss of heterozygosity (LOH) in human breast tumours) and applied to the gene expression data, in order to score each tumour for relative signature activity (yellow, more active). The PI(3)K panel includes a protein-based (RPPA) proteomic signature. Tumours were ordered first by mRNA subtype, although specific ordering differs between the panels. P values were calculated by a Pearson’s correlation or a Chi-squared test.

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