Biotech Values

[poorgradstudent]

ARQL / MET

I have to admit I was operating under the premise that the majority of oncogenic mutations to c-met were not yet known - either from a percentage of all oncogenic c-met mutations or from a percentage of of humans with a c-met mutated cancer. But your sentence above implies that the significant majority of mutations are known and listed - which is/would-be a surprise to me given how difficult it is to find something when you don't know what it looks like?

My comment was more that the type of mutations are known, not that every exact mutation is known. Let me just be clear about some of the nuances since they're important to the conclusion.

1. If you're talking about missense point mutations that do not change the length of the protein, then the methods used in the paper will capture them. So in this regard, the missense mutations need not be known to be captured.

2. If you're talking about mutations that change the length of the protein, cause re-arrangements between other genes and c-Met (a la bcr-abl) then they may or may not be captured by the methods used in the paper.

Therefore, if there are a significant number of identified missense mutations as defined by #1, and to date no examples that conform to #2, then it is not all that reasonable to base your argument solely on the existence of unknown mutations of the #2 variety.

Which is why I replied as I did. To my knowledge the majority of c-Met mutations are missense, and these often impact amino acids at the tyrosine kinase domain. All of these will be captured. I'm not aware of a mutation that truncates the protein in a manner imagined by Vinmantoo, so my position is that the data in the paper are reliable unless someone finds an example that conforms to Vinmantoo's imaginary protein.


Final point, the new paper I linked in the previous post makes it rather clear that this cell line does not express the protein. They generated another antibody that also came up blank in the TOV-112D*.



* For the record, Vinmantoo can design a c-Met protein that this last paper would also miss. So can I. But when designing your own proteins as reasons for a specific biological effect, I think the onus is on us to prove that they exist.