Mutations of POLE-exo* Group A mutants in the UCSC Genome Browser. The TCT→TAT and AGA→ATA mutations were taken from six whole-genome sequences of POLE-exo* mutant tumors from TCGA patients (F5-6814, AA-A00N, EI-6917, CA-6718, AA-3555, A6-6141). (A) POLE-exo* mutants TCT→TAT (red) or AGA→ATA (blue) from chromosome 17 (top tracks) and a representative segment zoomed in to show clustering of same-strand mutations. TCGA patient ID is to the left of the track. Note alignment of red and blue clusters preserved across multiple patients and clusters predominating in red and blue (boxes). Ordering of patient tracks is the same on top and bottom. (B) POLE-exo* mutations mapped to LMNB2 ORI. The ORI position is chromosome 19:2367825 to 2368428. (Top) Schematic of a replication origin showing leading strand and expected mutations from POLE-exo* mutants mapped to the reference strand. The turquoise bar indicates ORI location. (Bottom) C→A (red hash marks) predominate to the left of the ORI (17/26); C→A (16/60) are the minority to the right (χ2 P = 0.00164). (See also Supplemental Fig. S6 for well-characterized ORI at TOP1 and DHFR.)
