Variant calling on matched primary and metastatic tumor without normal samples.

Question

[Venados]

Hello!

I have exome sequencing data for 20 pairs of primary and matched metastatic tumors coming different patients. However, I have no Normal samples.

I am interested in looking at mutation evolution from the primary to metastatic samples. What would be the best strategy to call variants? The way I see it, I have two options:

1) Call variants using the primary sample as the control sample for their matched metastatic sample and use the metastatic sample as the normal for the primary sample.

2) Follow the TCGA workflow for Tumor-Only variant calling and just call the samples independently. https://docs.gdc.cancer.gov/Data/Bioinformatics_Pipelines/DNA_Seq_Variant_Calling_Pipeline/#tumor-only-variant-annotation-workflow

EDIT: Or would it make more sense to create a "Panel of Normals" for each patient using the matched primary and metastatic tumor?

I would like to hear your thoughts on how to approach this problem. thank you all in advance for the advice!!!

[Nicolas Rosewick]

I would try both options and compare them. However for option 1) I would use primary as control and metastatic as tumor.