Posts Tagged Mutations
Current sequencing efforts churn out massive amounts of (missense) mutations for a given reference genome – so cancer-cell lines are an obvious and worthy target for these shiny new big guns. Adressing the question of what these mutations are actually doing (wrong) and how they affect structure and function of proteins is not quite straightforward. The problem is that each tumor has a slightly different set of mutations, even parts of the same tumor might not be genetically identical. Are there detectable trends that would tell us more about the molecular mechanisms involved?
One could speculate about the dominant mode of action in tumor initiaition / progression at the molecular scale: For example, mutating a small, hydrophobic amino-acid in the core into a big, charged one might screw up the entire structure, rendering the protein inactive (loss-of-function). Alternatively, one could imagine how mutations at the surface alter binding affinity / specificity and cause havoc in the downstream signalling and regulatory pathways (gain-of-function).
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