In the following picture, you can see that in normal cells (yellow) we have two copies of each gene, while in tumor cells (violet), we just have one copy due to a clonal mono-allelic deletion. I do not really care about the genotype of the two genes, I just need to know that they are heterozygous.

enter image description here

On the other hand, suppose we are talking about somatic heterozygous SNVs and therefore we do not consider deletions anymore. In this case I would like to know the genotype (AA, AB or BB) of tumor and normal cells. Based on my understanding, I expect the AF of the SNVs in the tumor cells to be roughly 0.5 (since I ask for heterozygous SNVs). But what about normal cells? What is their genotype? If I ask for heterozygous SNVs, does that imply that normal cells are homozygous for that alleles?

  • $\begingroup$ Normal cells also have SNV and mutations, in fact recognizing which mutations and SNV are the ones that cause the tumor is an active research area. But it is impossible to say which is their genotype, as you would need to sequence them to know it. $\endgroup$
    – llrs
    Jun 12, 2018 at 7:03

1 Answer 1


Your initial information/image and actual question seem pretty unrelated to me, but I'll do what I can.

If you have a heterozygous SNV in a malignant population of cells, it really depends on when the mutation occurred for you to know the genotype of wildtype cells. It could have been there since birth (a germline mutation passed down from the parents) or have been acquired throughout the person's life and clonally expanded (somatic mutation).

Unfortunately, you have no way to differentiate between these two types of SNVs just by sequencing the tumor cells. If you want to know true somatic mutations that are found only in the tumor cells, you need to sequence a matched normal control from the same patient (preferably from the same cell type). This is why most large cancer sequencing studies include not only tumor samples, but normal cells from the same patient - see TCGA or ICGC for examples.


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