Question: how to interprete the somatic mutations with low frequency in tumor sample compared with the normal one
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gravatar for Ontheway
3.0 years ago by
Ontheway10
Ontheway10 wrote:

I have matched pair samples: tumor and normal sample. I used varscan and mutect to call the somatic variants and found that most of mutations have low mutation frequencies, 1%~5%. Are they normal? or the tumor sample are impure? or the tummor has a high heterogeneity ?

hope to get a reply, Thank you !

cancer genomics • 1.0k views
ADD COMMENTlink modified 3.0 years ago by igor8.3k • written 3.0 years ago by Ontheway10
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gravatar for poisonAlien
3.0 years ago by
poisonAlien2.8k
Asgard
poisonAlien2.8k wrote:

In short, all of your reasons are possible, including maybe due sequencing errors. But if your depth is high enough you can be little bit confident in calling them as true somatic events. You should also check ExAC for rare SNPs.

ADD COMMENTlink written 3.0 years ago by poisonAlien2.8k
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gravatar for igor
3.0 years ago by
igor8.3k
United States
igor8.3k wrote:

What is the coverage? For example, if it's 20X, then 5% is just 1 read, so probably not real.

Did you visually inspect the mutations in a genome browser like IGV? Do the reads and variants look clean? Anything visual is hard to explain, but after you see a few high-quality variants, it should be relatively easy to spot bad calls.

Ultimately, it's not really possible to tell if the mutation is real. You really need to validate by sequencing the samples again. It's very common that even high quality mutations that get called by multiple variant callers and look very good by visual inspection do not validate.

ADD COMMENTlink written 3.0 years ago by igor8.3k
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