Explaining relation of WGS and transcriptome

Question

[zizigolu]

Hi

I have a RNA-seq data comparing responders to chemotherapy and non-responders

I am seeing CDKN2A (a tumour suppressor) has been significantly deleted in non-responders (by GISTIC); I then expect that CDKN2A be down regulated in non responders RNA-seq but I am seeing the swap way, CDKN2A is being up-regulated in non-responders

My confusion is, how a gene is being deleted from chromosome but RNA-seq shows this genes is being up regulated in RNA-seq

Thank you for any information

Answer 1

[swbarnes2]

There might be a few explanations. Off the top of my head, I could imagine a partial deletion impairing function, and the cell trying to compensate by attempting to transcribe more of it. More transcription in this case not leading to more functional protein operating.

You might look at downstream genes, see if those are down-regulated.

[zizigolu]

Thank you, CDK6 is downstream of CDKN2A

CDKN2A is a suppressor of CDK6

I am seeing CDK6 is being down regulated in non responders that means CDKN2A should be up regulated while in WGS I see CDKN2A is being deleted This is really confusing