Question: Driver And Passenger Mutations In Cancer
3
gravatar for kanwarjag
7.0 years ago by
kanwarjag1.1k
United States
kanwarjag1.1k wrote:

I am trying to understand how we can specify that a particular mutation is driver but other is not. I have read http://cancerres.aacrjournals.org/content/68/6/1675.full.pdf+html but is there any tool - web based/ command line, where if we have data from tumor vs matched normal, I should be able to specify these mutations. What criteria suggest that it is driver and not passenger.

Thanks

mutation • 7.2k views
ADD COMMENTlink modified 7.0 years ago by Hayssam280 • written 7.0 years ago by kanwarjag1.1k
6
gravatar for Chris Miller
7.0 years ago by
Chris Miller21k
Washington University in St. Louis, MO
Chris Miller21k wrote:

This is not a simple or solved problem. In fact, it's one of the greatest challenges facing the field today. Perhaps the most robust way to find drivers is leveraging large cohorts of samples and using recurrence as an indicator of selection (relevant methods: the SMG test in MuSiC or MutSig). Another is to use functional annotation to infer driver status. If a mutation activates a kinase, or alters a gene in a tumor-suppressor pathway, it's possibly important.

That said, there are undoubtedly a large number of rare mutations that contribute to oncogenesis that have not been discovered or understood. As I said, it's a very difficult problem.

ADD COMMENTlink modified 7.0 years ago • written 7.0 years ago by Chris Miller21k
3
gravatar for Matt Shirley
7.0 years ago by
Matt Shirley9.4k
Cambridge, MA
Matt Shirley9.4k wrote:

Quick, before anyone answers this question make sure to publish your answer in a high-profile journal for fame and fortune!

ADD COMMENTlink written 7.0 years ago by Matt Shirley9.4k
2
gravatar for Biojl
7.0 years ago by
Biojl1.7k
Barcelona
Biojl1.7k wrote:

I think you'll be very interested in this research group methods and tools

They've recently published a series of very relevant papers related to your question.

ADD COMMENTlink written 7.0 years ago by Biojl1.7k
2
gravatar for Hayssam
7.0 years ago by
Hayssam280
France
Hayssam280 wrote:

Hi, to follow up a bit on Chris' answer, I would add a semantic twist to your question:

  • Short answer : Use databases indicating whether a mutation can be a driver, e.g. COSMIC etc.
  • intermediate answer : You can't answer your question just by observation
  • Long answer : You can determine whether you have sufficient evidence to consider that a mutation is likely a driver mutation (e.g. if it's significantly often mutated in cancers), but that'll always only be evidence for follow-up experiments, where you'll e.g. induce the specific mutation and e.g. observe proliferation advantages. Apart from that, you can only recover indications that a gene / mutation might be driver.

The review by Bert Vogelstein and the Hallmarks of cancer papers can help you clarify this as well as give additional definitions and indications.

ADD COMMENTlink modified 7.0 years ago • written 7.0 years ago by Hayssam280

I find it amusing that your short answer is longer than your intermediate answer. :) Yes, good advice on using COSMIC and other DBs. Worth noting that they also do a really good job of making artifacts look significant - so be cautious.

ADD REPLYlink written 7.0 years ago by Chris Miller21k
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