POLE and central nervous system cancer: Using WES and a linkage-based strategy (Additional file 1: Table S1), the POLE:c.139C>T p.(R47W) variant was identified as the only rare (MAF ≤ 0.01) deleterious germline variant, not present in controls and located in a cancer predisposition gene, co-segregating with the glioma phenotype in index tumor family Fam011 with two glioma patients and a colorectal carcinoma patient in three consecutive generations (Fig. 1a; Table 1).