Fig. 4: UV damage begins before malignant transformation.

a, Subway plot showing clonal dynamics, clinical features and the disease course of patient 10. Samples profiled by WES (n = 5) are indicated by black dots and connected according to phylogenomic relationships. The line width indicates the total number of detected mutations in each sample, and the colour indicates the percentage of UV-associated TC>TT mutations from green (0%) to orange (50%). The plots at the bottom show the bone marrow blast count (left y axis, black lines) from pathology assessment, and donor chimerism (right y axis, grey line) after allogeneic stem-cell transplant. b, VAFs (y axis) of somatic mutations (x axis) detected in uninvolved bone marrow (top) and two BPDCN skin tumours from distinct anatomical sites (middle and bottom) in patient 10 at diagnosis, as in a. Mutations are grouped according to the sample in which they were first detected (left, bone marrow; middle left, shared skin 1 and 2; middle right, unique to skin 1; right, unique to skin 2). UV-associated TC>TT mutations are indicated in orange, and other mutations are indicated in green. The hashes indicate mutations of which VAFs are affected by copy-number alterations or ___location on chromosome X. c, Normalized read coverage on chromosome 9 for the two BPDCN skin tumours presented in a and b. Separate homozygous deletions affecting the CDKN2A tumour suppressor gene are indicated, with vertical bars showing the read coverage in the deleted (red bars) and non-deleted (blue bars) regions. d, Phased B allele frequencies (y axis) of heterozygous SNVs on chromosome 3 for the two BPDCN skin tumours presented in a–c. The vertical bars indicate the allele frequencies in a region containing the SETD2 tumour suppressor gene. Blue bars, A allele lost; red bars, B allele lost.