I am planning an experiment whereby I treat cancer cells with increasing amounts of drug over many passages. I aim to identify cells that ultimately become resistant to the drug at concentrations that are lethal to non-drug treated control cells. I've been thinking about possible experiments involving whole genome sequencing and phospho-proteomic analysis. If I wanted to identify a resistance mutation, would it be possible to identify oncogene by just comparing the non-treated and drug-resistant lines by genome sequencing?
Yes, sequencing will show deletions. Do Histone methylation profiling in addition to pick up repressed or expressed genes.
I do not think that by genome sequencing you would be able to distinguish resistant from non resistant cells.
But the comparative analysis between the genome of a resistant and a non resistant cell will permit you identify if there are mutations.This does not mean that these mutations are the cause of resistance.
On the other hand you will find the overexpression of many drug transporters that are related with resistance and with no genetic mutation.
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