POLE and cancer: The PLS-PM model was constructed with the 13 DDR genes associated with higher TMB/neoantigen loads (germline or somatic regression coefficient > 1.5 and FDR < 0.05 in any cancer type), including multiple HR (BRCA1/2, PALB2), MMR (MLH1, MSH2, MSH3, MSH6, and PMS2), damage sensor (ATM, ATR, and CHEK2), and DNA polymerase (POLE, POLQ) genes (Figure 2D).