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Fig. 1 | Genome Medicine

Fig. 1

From: Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma

Fig. 1

Study workflow and mutational intra-tumor heterogeneity. a Study workflow presenting the anatomical sites selected for the multi-sampling procedure and related molecular analysis showing the patient series size and sample selection. b Heatmap of the cancer-related gene variants with damaging consequences detected in paired biopsies and derived primary cell lines. The legend in the bottom left indicates the color codes used in the heatmap. Intra-tumor heterogeneous variants are framed in blue. c Mutational intra-tumor heterogeneity. Trees schematically illustrate the cancer-related gene variants with damaging consequences detected in paired biopsies and derived primary cell lines of the four patients displaying intra-tumor heterogeneity at the genetic level. Solid lines are for paired biopsies and dotted lines for primary cell lines (CL). d Clonality of the variants with structural consequences detected in tumor samples from patient T333HP. On the left, the graph shows the adjusted cancer cell fraction (CCF) values of each protein variant, validated using IGV visualization. Each variant was then categorized according to its clonality (clonal when present in all cells of a sample) as well as to its spatial segregation (shared when present in the two biopsies, private otherwise) and was colored according to its clonality status. Cancer-related genes are indicated. Subclonal variants only present in a fraction of cancer cells but in both paired biopsies are surrounded by a red circle and might be consistent with the polyclonal diffusion of these tumors throughout the thoracic cavity. On the right, the clonal evolution is schematically represented as a tree. For subclonal populations, the line width is proportional to the number of variants

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