Finally, in addition to identifying signatures of concurrent POLE-exo* and MMR deficiency, we found an additional signature (designated as signature D1) that was highly active (>1000 mutations and >30% of mutation burden) in 4/10 MSI-H tumors that also had a mutation in the exonuclease domain of POLD1 (Fig. 4a, b). The gene discussed is POLE; the disease is mismatch repair cancer syndrome 1.