Somatic SNVs vs. Germline SNPs for allele-specific copy number analysis
0
0
Entering edit mode
3.6 years ago
vctrm67 ▴ 50

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 • 1.4k views
ADD COMMENT
1
Entering edit mode

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 REPLY
0
Entering edit mode

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

ADD REPLY
0
Entering edit mode

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 REPLY
0
Entering edit mode

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

ADD REPLY
1
Entering edit mode

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 REPLY
0
Entering edit mode

What about germline SNVs (not SNPs)?

ADD REPLY
0
Entering edit mode

Germline SNVs are SNPs

ADD REPLY
0
Entering edit mode

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 REPLY
1
Entering edit mode

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 REPLY

Login before adding your answer.

Traffic: 2018 users visited in the last hour
Help About
FAQ
Access RSS
API
Stats

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.

Powered by the version 2.3.6