Fig. 4: Correlation between oncogenic genomic alterations and protein expression/activation in patients with progressive disease.
Unsupervised hierarchical clustering analysis using Wardās method of members of the PI3K/AKT/mTOR signaling pathway shows increased activity and clustering of tumor epithelia collected from patients that developed disease progression (a). NGS-based analysis of the recurrent lesions at disease progression for three of the four patients with progressive disease identified an oncogenic mutation of PIK3CA in one patient and amplification of the CCND1 gene in the remaining two patients (b). Increased activation levels of AKT and mTOR detected in patients with progressive disease did not correlate with the underlying genotype (cāe). Similarly, the expression of Cyclin D1 did not directly correlate with CCND1 amplification (f).
