These authors contributed equally to this study.
Parallel evolution of tumour subclones mimics diversity between tumours
Article first published online: 9 JUL 2013
© 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
The Journal of Pathology
Volume 230, Issue 4, pages 356–364, August 2013
How to Cite
Martinez, P., Birkbak, N. J., Gerlinger, M., McGranahan, N., Burrell, R. A., Rowan, A. J., Joshi, T., Fisher, R., Larkin, J., Szallasi, Z. and Swanton, C. (2013), Parallel evolution of tumour subclones mimics diversity between tumours. J. Pathol., 230: 356–364. doi: 10.1002/path.4214
No conflicts of interest were declared.
- Issue published online: 9 JUL 2013
- Article first published online: 9 JUL 2013
- Accepted manuscript online: 28 MAY 2013 12:37PM EST
- Manuscript Accepted: 22 MAY 2013
- Manuscript Revised: 17 MAY 2013
- Manuscript Received: 7 SEP 2012
|path4214-sup-0001-FigureS1.tif||TIFF image||1502K||Copy-neutral loss of heterozygosity in patient RK21. Segmented copy number of the major (red) and minor (blue) alleles in chromosome 3|
|path4214-sup-0002-FigureS2.tif||TIFF image||2880K||Hierarchical clustering of 143 stage III and IV TCGA samples and 48 multi-region samples from eight patients. Heat map columns represent samples and are ordered to match the dendrogram, while rows represent cytobands. Horizontal bars delimit chromosomes. The hierarchical clustering is based on Spearman's rank correlation coefficient between samples. The colour coding indicates the relative copy number of each cytoband in each sample. Significant clusters obtained using 1000 bootstrapping iterations are highlighted by bars below the copy number profiles of the relevant samples, using alternating grey and black for clarity. Multi-region samples are highlighted and reported below the significant clusters bar|
|path4214-sup-0003-FigureS3.tif||TIFF image||3064K||Hierarchical clustering of 440 TCGA samples and 48 multi-region samples from eight patients. Heat map columns represent samples and are ordered to match the dendrogram, while rows represent cytobands. Horizontal bars delimit chromosomes. The hierarchical clustering is based on Euclidean distances between samples. The colour coding indicates the relative copy number of each cytoband in each sample. Significant clusters obtained using 1000 bootstrapping iterations are highlighted by bars below the copy number profiles of the relevant samples, using alternating grey and black for clarity. Multi-region samples are highlighted and reported below the significant clusters bar|
|path4214-sup-0004-FigureS4.tif||TIFF image||10269K||Model-based clustering of 440 TCGA samples and 48 multi-region samples from eight patients with hmmMix. Cluster profiles are shown on top, green indicates copy number loss and red indicates copy number gain. Clusters and samples are shown below with horizontal white bars separating the clusters, along with delimiting vertical coloured bars on the left. Samples within a cluster are ordered as they were prior to hmmMix computation. Multi-region samples are highlighted by the coloured bar on the left, indicating from which patient they originate|
|path4214-sup-0005-FigureS5.tif||TIFF image||4204K||Network representation of relationships between multi-region and stage III and IV. TCGA samples using Euclidean distances. Samples are represented as nodes (diamonds for stage III samples, circles for stage IV) and Euclidean distances are used to weight the edges connecting them. The network is fully interconnected and all edges are used to create the layout. Only edges corresponding to distances significantly smaller than expected (including the bottom 5% of the unrelated samples distance distribution) are drawn with thick lines. Coloured lines highlight connections between samples from the same tumour; black lines are used for unrelated samples; white node labels indicate regions from untreated tumours; black node labels indicate regions from treated tumours|
|path4214-sup-0006-FigureS6.tif||TIFF image||1758K||Overall copy-number profiles of all samples used in the hierarchical clustering analysis. The plain black line represents the median copy number of each cytoband across all samples. Vertical bars specify chromosome starts (plain lines) and centromeres (dashed lines). Blue dots indicate cytobands located on a chromosomal arm lost in more than 20% of all TCGA samples and red dots indicate those on arms gained in more than 20% of all TCGA samples|
|path4214-sup-0007-FigureS7.tif||TIFF image||906K||Expression of genes impacted by recurrent, large copy number aberrations. Normalized gene expression data were obtained from RNA-seq data on the TCGA website, using the 400 samples for which SNP array data were also available. A large aberration was considered present if at least half of the chromosome arm was gained or lost, absent otherwise. The expression of all genes on each analysed chromosome arm was compared between samples presenting the aberration and samples where it was considered absent. Gene expression distribution are displayed with box plots, green for normal samples, red for samples showing a gain (left) and blue for samples showing a loss (right). p values were obtained using a two-tailed t-test|
|path4214-sup-0008-TableS1.doc||Word document||30K||Patient clinical and pathological data|
|path4214-sup-0009-TableS2.doc||Word document||58K||List of the samples most similar to each multi-region profile, as defined by smallest correlation-based and Euclidean distances|
|path4214-sup-0010-TableS3.doc||Word document||55K||Number of significantly similar samples|
|path4214-sup-0011-TableS4.doc||Word document||64K||Number of large aberrations (involving at least half of the length of a chromosome arm) per multi-region sample and number of average vs ubiquitous number of aberrations per patient|
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