Linkage of genetic drivers and strain-specific germline variants confound mouse cancer genome analyses

Mueller, S., Lange, S., Collins, K. A. N., Krebs, S., Blum, H., Schneider, G., Rad, L., Saur, D., Rad, R. (2020). Nat Commun 11, 4474.

DOI:10.1038/s41467-020-18095-3(link is external)


Niknafs et al. describe evolutionary trajectories in pancreatic cancer using mouse models with engineered KrasG12D and Trp53R172H mutations (KPC model). As an additional aspect, the study reports frequent homozygous deletions at the Nlrp1 locus, which are interpreted as a somatic driver event in pancreatic cancer. We observed that the origin of this Nlrp1 alteration is strain-specific germline variation, having profound impact on the interpretation of its biological relevance. Beyond this specific locus, we show that strain-specific germline variation is a general confounder of genome analyses in mouse models of cancer.