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. 2023 Mar 28;13(6):1364–1385. doi: 10.1158/2159-8290.CD-22-1427

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©2023 The Authors; Published by the American Association for Cancer Research

This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.

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Figure 3. Late-emerging brain metastases have a lower copy-number burden. A, wGII per metastatic site. Site-specific null distributions of mean wGII were generated by randomizing sample sets (from any metastatic site) while keeping patient contributions constant (see Methods). **, P ≤ 0.01. Leptomen., leptomeninges. B, Correlation between brain copy-number (CN) distance to other sites and time of emergence of brain metastases after stage IV diagnosis in days. C, Growth dynamics of tumors in patient CRUKP5107. The brain lesion (in orange) was detected in only the last two scans after the targeted therapy [BRAF inhibitor (i) + MEKi], ICI (PD-1i + CTLA4i), and chemotherapy courses. PD, progressive disease; PR, partial response; SD, stable disease. D, SNV and indel phylogenetic tree of tumor clones in patient CRUKP5107. E, The mutational signature contributions to each clone in the phylogeny in D are shown. MMR, mismatch repair. F, The anatomic distribution of clones. Each pie chart represents a sample with its clonal composition indicated by the colors. A multiregional sampling of the same tumor is indicated by the gray dashed lines. BR, brain; LI, liver; LU, lung; PC, pericardium; ST, soft tissue. — Late-emerging brain metastases have a lower copy-number burden. A, wGII per metastatic site. Site-specific null distributions of mean wGII were generated by randomizing sample sets (from any metastatic site) while keeping patient contributions constant (see Methods). **, P ≤ 0.01. Leptomen., leptomeninges. B, Correlation between brain copy-number (CN) distance to other sites and time of emergence of brain metastases after stage IV diagnosis in days. C, Growth dynamics of tumors in patient CRUKP5107. The brain lesion (in orange) was detected in only the last two scans after the targeted therapy [BRAF inhibitor (i) + MEKi], ICI (PD-1i + CTLA4i), and chemotherapy courses. PD, progressive disease; PR, partial response; SD, stable disease. D, SNV and indel phylogenetic tree of tumor clones in patient CRUKP5107. E, The mutational signature contributions to each clone in the phylogeny in D are shown. MMR, mismatch repair. F, The anatomic distribution of clones. Each pie chart represents a sample with its clonal composition indicated by the colors. A multiregional sampling of the same tumor is indicated by the gray dashed lines. BR, brain; LI, liver; LU, lung; PC, pericardium; ST, soft tissue.