Question: Somatic SNVs vs. Germline SNPs for allele-specific copy number analysis
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gravatar for vctrm67
6 weeks ago by
vctrm6720
vctrm6720 wrote:

To my understanding, one needs the B-allele frequencies for allele-specific copy number. To get those, you usually use germline SNPs for the following reason:

"In this context, the b allele is the non-reference allele observed in a germline heterozygous SNP, i.e. in the normal/control sample. Since the tumor cells' DNA originally derived from normal cells' DNA, most of these SNPs will also be present in the tumor sample. But due to allele-specific copy number alterations, loss of heterozygosity or allelic imbalance, the allelic frequency of these SNPs may be different in the tumor, and that's evidence that one (or both) of the germline copies was gained or lost during tumor evolution."

However, is there anything wrong with using somatic SNVs as well? Somatic SNVs are confirmed heterozygous sites that should give the same insight into frequencies of the non-reference allele, right?

cnv • 173 views
ADD COMMENTlink written 6 weeks ago by vctrm6720
1

is there anything wrong with using somatic SNVs as well?

There will be a lot less of them, so the impact will be negligible.

ADD REPLYlink written 6 weeks ago by igor11k

But wouldn't it be better to use both somatic SNVs and germline SNPs even still?

ADD REPLYlink written 6 weeks ago by vctrm6720

With germline, you know the original frequency is either 50% or 100%. With somatic, you do not. As you said, somatic variants are still informative. They can be used to estimate tumor purity and clonality, and there are specialized tools for that.

ADD REPLYlink modified 6 weeks ago • written 6 weeks ago by igor11k

When you say "With somatic, you do not", so it is because of tumor purity and clonality that deviate this?

ADD REPLYlink written 6 weeks ago by vctrm6720
1

Yes. You also don't know the absolute copy number. For example, if the variant is at 25%, it could be 25% tumor (homozygous), 50% tumor (heterozygous), amplification of the non-mutated copy (1 mutant, 3 WT), some combination of those, or a more complex event.

ADD REPLYlink modified 6 weeks ago • written 6 weeks ago by igor11k

What about germline SNVs (not SNPs)?

ADD REPLYlink written 6 weeks ago by vctrm6720

Germline SNVs are SNPs

ADD REPLYlink written 6 weeks ago by igor11k

My mistake. I thought the distinction was SNPs are found within a certain percentage of the population, whereas germline SNVs could still be below that percentage.

ADD REPLYlink written 6 weeks ago by vctrm6720
1

For the purpose of somatic/germline discussion, any germline/inherited SNV is a SNP and tumor-specific is somatic. For population genetics, you can have common and rare SNPs. They are germline either way.

ADD REPLYlink written 5 weeks ago by igor11k
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