American Society of Hematology

Figure 4.

$SV and chromothripsis involve very large, complex events in TP53-mutated myeloid malignancies. (A) Somatic SV call counts for each case. Counts colored per SV classification: breakends (BND), deletion (DEL), duplication (DUP), insertion (INS), and inversion (INV). (B) Distribution of somatic SV cluster sizes for each case. Counts colored per the number of individual SV events occurring within the corresponding complex SV cluster. (C) Frequency of somatic SV breakpoints in 100-Kb windows genome wide. Bar height indicates the fraction of samples with at least 1 SV breakpoint within each window. (top) Fraction of CBF AML with somatic SV breakpoints in each window. (bottom) Fraction of TP53-mutant AML with somatic SV in each window. In CBF AML, enrichment of breakpoints is clearly present at inv(16) and t(8;21) positions. Breakpoints are present throughout the genome in TP53-mutated AML/MDS cases, with enrichment on chr17 and chr21. (D) Large regions of chr5, chr12, chr16, and chr17 are involved in complex rearrangements affecting copy number, including the TP53 genomic locus in a case of TP53-mutated AML (UPN 983349). (Outer track) copy gains (blue) and losses (red). (Inner track) regions involved in high-confidence chromothripsis events (dark blue). Gray arcs indicate novel adjacencies created by structural rearrangements. (E) Chromothripsis is detectable in 60% of TP53-mutated myeloid malignancies and is not present in any CBF AML cases. (F) Genome-wide distribution of high-confidence chromothripsis calls. Proportion of all TP53-mutated PCAWG (top; n = 623) and AML/MDS (bottom; n = 42) samples with a chromothripsis call on each chromosome.$

SV and chromothripsis involve very large, complex events in TP53-mutated myeloid malignancies. (A) Somatic SV call counts for each case. Counts colored per SV classification: breakends (BND), deletion (DEL), duplication (DUP), insertion (INS), and inversion (INV). (B) Distribution of somatic SV cluster sizes for each case. Counts colored per the number of individual SV events occurring within the corresponding complex SV cluster. (C) Frequency of somatic SV breakpoints in 100-Kb windows genome wide. Bar height indicates the fraction of samples with at least 1 SV breakpoint within each window. (top) Fraction of CBF AML with somatic SV breakpoints in each window. (bottom) Fraction of TP53-mutant AML with somatic SV in each window. In CBF AML, enrichment of breakpoints is clearly present at inv(16) and t(8;21) positions. Breakpoints are present throughout the genome in TP53-mutated AML/MDS cases, with enrichment on chr17 and chr21. (D) Large regions of chr5, chr12, chr16, and chr17 are involved in complex rearrangements affecting copy number, including the TP53 genomic locus in a case of TP53-mutated AML (UPN 983349). (Outer track) copy gains (blue) and losses (red). (Inner track) regions involved in high-confidence chromothripsis events (dark blue). Gray arcs indicate novel adjacencies created by structural rearrangements. (E) Chromothripsis is detectable in 60% of TP53-mutated myeloid malignancies and is not present in any CBF AML cases. (F) Genome-wide distribution of high-confidence chromothripsis calls. Proportion of all TP53-mutated PCAWG (top; n = 623) and AML/MDS (bottom; n = 42) samples with a chromothripsis call on each chromosome.

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