Fig. 4

CNA and SNV analyses by whole-genome, targeted, and whole-exome sequencing and its validation by single-molecule deep sequencing reveal three different subclones of the cancer tissue. a After performing low-depth whole-genome sequencing (0.16 Gb/sample), CNA was determined as described in the “Methods” section. Rows were reordered to cluster samples by the correlation of their CNAs. Excluding the tumor and normal bulk, we found three distinct genetic subclones. The three subclones had both shared and exclusive CNA events. b The correlation matrix of the copy number data also produced the three subclones. Unsupervised clustering was used for reordering of the samples. c Targeted sequencing of the 53 isolated cell clusters. As in the CNA analysis, we found three distinct genetic subclones. The three subclones had unique somatic mutation patterns. d Whole-exome sequencing of 4 samples from each subclone. Subclones 1 and 3 shared a large portion of mutations, including the PIK3CA mutation. e Spatial mapping of genomic data showing that each subclone is spatially segregated, with stroma between each subclone