Fig. 1: Chromothripsis-associated chr. 21amp is a recurrent and adverse prognosis genome amplification event in BP-MPN.
a, Study overview. b, log R ratio plot of chromosome 21 derived from SNP karyotyping assay (DNACopy analysis) showing chromothripsis of chromosome 21 (’chr. 21amp’) in a representative case of BP-MPN. SNP karyotyping performed for n = 64 samples. c, Graphic displaying the MAR in common across all chr. 21amp cases (n = 16). d, Boxplot of median/interquartile range (IQR) of CN overlying the chr. 21amp MAR for all cases (n = 16, the lower and upper hinge correspond to the IQR (25th and 75th percentiles), with the upper and lower whiskers extending from the hinge to ±1.5 × IQR). e, GISTIC analysis of recurrently lost (blue) and amplified (red) focal regions across all cases. Green horizontal line depicts the false discovery rate (FDR)-adjusted Q value threshold of 0.05 (n = 64). f, Boxplot of median/IQR (as in d) showing that chr. 21amp cases have a greater number of non-chr. 21 CN abnormalities compared with non-chr. 21amp cases (median 6.5 (IQR 4–10.3) versus median 1 (IQR 1–5), P = 0.0001 by two-sided Wilcoxon rank-sum test). g, Heatmap shows Pearson correlation coefficient of myeloid mutations and most frequent CNAs. Purple denotes positive co-variance, yellow negative; *Padj < 0.05. h, Kaplan–Meier analysis of patients with BP-MPN stratified by presence/absence of chr. 21amp event. Schematic in a created using BioRender.com. eLRR, estimated log R ratio; Mb, megabase.
