POLE and mismatch repair cancer syndrome 1: We found signatures caused by genetic defects were more frequent in AYAs than in OAs (Fig. 4d, Supplementary Data 8), including signatures caused by BRCA1/2 mutations (3.8% vs. 1.8%), MMR deficiency (54.1% vs. 36.9%), and POLE/D mutations (6.1% vs. 2.7%).