Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia [Exome-seq]

Aim: assess the contribution of de-novo clonal mutations to the observed adaptive behaviours to nutrient starvation in PDX derived melanoma and lung cancer cells. Methods: Identical replicates from both cancer models were plated in 96 wells plates and grown in starvation (RPMI media lacking L-glutamine). After prolonged exposure to starvation, extensive phenotypic variability was observed. We selected populations that managed to adapt (t20 samples, strong but also moderate phenotypes) and performed exome-seq. Comparison of their mutational landscape with the initial parental populations (t=0) will uncover possible candidates that drive the adaptation of these populations. Results: Absence of any selected clonal mutation within individual resistant populations or recurrent subclonal mutations across replicates Conclusions: The stochastic adaptive behaviours observed upon starvation in PDX MeA5a and L1C5c derived lines does not seem to be confered through selection of clonal genetic events. Exome-seq in 10 populations (5x Melanoma, 5x NSCLC). Comparison with the mutational landscape of the parental populations before nutrient starvation (DAY O samples)