D402A : Tumor susceptibility and immune response in mouse models

Homozygosity for the Pold1^D400A mutation mimicking human POLD1-D402A causes cancers with high mutational burden and improved response to immune checkpoint blockade in mousemodels. Heterozygous Pold1^+/D400A mice do not show a tumor phenotype.

References

Goldsby, R.E. et al. Defective DNA polymerase-δ proofreading causes cancer susceptibility in mice. Nat Med 7, 638-639 (2001). https://pubmed.ncbi.nlm.nih.gov/11385474/
Goldsby, R.E. et al. High incidence of epithelial cancers in mice deficient for DNA polymerase δ proofreading. Proc Natl Acad Sci USA 99, 15560-15565 (2002). https://pubmed.ncbi.nlm.nih.gov/12429860/
Sawant, A., et al. Immune checkpoint blockade delays cancer development and extends survival in DNA polymerase mutator syndromes. Cancer Res 85, 1130-1144 (2025). https://pubmed.ncbi.nlm.nih.gov/39786467/