Simple question about deleted genes

Question

[Avro]

Hi everyone,

I have a simple question about aCGH data: if you have two copies per gene and your log2 ratio is cancer/normal, how can you observe log2 = -4? That means 1/16... 16 original copies? I understand log2 = -1 (1/2).

Thank you!

Answer 1

[Devon Ryan]

That means a 16th of the normal number of alleles that you would normally have detected. Remember that this is an average of a heterogeneous tissue, so some cells will have 2 copies, some 0, some 1, etc.

[Avro]

Hi Devon, Thank you for your quick response. I understand now! Basically, it is the cells with 0 copies that bring the ratio very low, right? Essentially, a cell can either have 0,1,or 2 copies. As for 1/2, then is it safe to suggest that cells are hemizygous (i.e. physical loss of one allele)? I don't think so...

The same can be said about amplifications, right?

Thank you!

[Devon Ryan]

A log2 of -1 would suggest that the average copy number is 1. Whether all/most of the cells are hemizygous or you have 2 populations, one with 2 copies and the other with 0, is undetermined.

Yes, the same is the case for amplifications.

[Avro]

Thanks!

I am making a presentation about the thresholds that I am using. I could write it in terms of % increase or decrease, no? For example: "The minimal thresholds used were 0.1 (amplifications) and -0.1 (deletions). This translates to 1.07 (2^0.1) and 0.93 (2^-0.1). Essentially, an allele is considered to be amplified if its total copy number is increased on average by 7% in the cancerous tissue relative to the normal tissue. The opposite is true for deletions."