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. 2023 Mar 1;14:1157. doi: 10.1038/s41467-023-36801-9

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — a Unsupervised cluster analysis of 1,689 tumor samples (columns) from METABRIC dataset²⁹ and the 150 DNA-based signatures scores (rows). Orange and violet colors represent scores above and below the median value of the signature across the dataset. Below the array tree, the InctClust classification²⁹ and the PAM50 molecular subtypes are shown for each sample. The predictor of the 4 clusters, which was derived from plasma ctDNA data in the Plasma-1 cohort (see Fig. 4), was applied in METABRIC and the results for each sample are shown below the data matrix. b Heatmap of signals from individual chromosomic regions found significantly associated with each cluster 1-4. Differentially represented segments were determined using a multi-class SAM analysis (FDR < 5%) c PAM50 molecular subtype distribution across the 4 DNA-based clusters in 1689 breast tumors of the METABRIC dataset²⁹. d TP53 mutation distribution across the 4 DNA-based clusters in 1,517 breast tumors of the METABRIC dataset²⁹. e Kaplan-Meier curves of DFS (left) and OS (right) of the 4 DNA-based clusters assessed in all tumors (n = 1689) (DFS Log Rank p = 3.51e-10; Cluster 1 vs 3 p < 0.001; OS Log Rank p = 1.56e−09; Cluster 1 vs 3 p < 0.001) and HR+/HER2- tumors (n = 1131) (DFS Log Rank p < 0.001; Cluster 1 vs 3 p < 0.001; OS Log Rank p < 0.001; Cluster 1 vs 3 p < 0.001) of the METABRIC database²⁹. Source data are provided as a Source Data file.