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. 2021 Mar 19;12:1751. doi: 10.1038/s41467-021-21798-w

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© The Author(s) 2021, corrected publication 2021

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. 1 — A Pleural mesothelioma tissue sampling locations were consistent between patients involving the apex (region1, R1), the pericardium (R2), anterior costophrenic angle (R3), posterior costophrenic angle (R4) and the oblique fissure (R5). The rationale for selecting the anatomically sterotyped sites at the time of tissue sampling was to ensure maximum coverage of the tumour from superior to inferior; medial to lateral; and anterior to posterior. We chose the oblique fissure (R5) as this is common to both the right and left lung and could be a reliable anatomical site bilaterally. Spatial evolution of mesothelioma would be expected to be best reflected in samples at maximum distance from one another, reflecting the inherent intratumour heterogeneity. These regions are represented by the most superior region (R1) and the inferior (R3 and R4). B Inter-patient and intratumour heterogeneity in the MEDUSA22 cohort. Histograms summarising the variance in clonal versus subclonal mutations (left) compared with somatic copy number alterations (SCNAs, right). Left top, relative number of mutations, left bottom, proportion of mutations ranked by clonal mutation proportion ranging from maximum (left) to minimum (right). Right top, ratio of truncal SCNA versus branch SCNA. Right bottom, relative proportion of SCNA ranked as for mutations. C Spectrum of subclonal diversity in the MEDUSA22 cohort, ranging from linear topology (MED33 left) to branched (MED12 right). Centre, Pie chart showing the relative proportion of patients in the MEDUSA22 cohort classified as either linear (64%) or branched (36%). D Box plots showing the positive correlation between topology classified as either linear or branched, and subclonal SCNA count (two-sided Mann–Whitney U test p = 0.034, left) and subclonal mutation count (two-sided Mann–Whitney U test p = 0.003, right). n = 22 patients. Both box plots denote medians (centre lines), 25th and 75th percentiles (bounds of boxes), and minimum and maximum (whiskers).