Fig. 2

DNA aberrations reflect the type of genomic instability. a We investigated the frequencies (vertical axes) of SNVs in each of six categories (indicated in the top panels) grouped according to sequence motif (flanking nucleotides are indicated on the horizontal axes). MSI cell lines (n = 8, excluding DLD1 and HCT15) and the POLE mutated cell line HCC2998 displayed different mutation signatures associated with the respective types of hypermutation. The MSI cell lines DLD-1 and HCT15 had a distinct mutation signature with a combination of deficient mismatch repair and POLD1 mutation. b Overview of detected SNVs/indels in 37 genes included in the Cosmic Cancer Gene Census and that were mutated in at least four MSI cell lines or one MSS cell line among the 27 cell lines analyzed by targeted deep sequencing. Most genes showed clear mutation frequency differences between MSS and MSI/POLE mutated cell lines. c There was an inverse relationship between the CNA load (horizontal axis; percent of basepairs with aberrant copy number) and the SNV/indel load (vertical axis) in the cell lines, reflecting their molecular subtype, as indicated. The neuroendocrine cell line Colo320 (green circle) grouped along with the MSS cell lines, and had few SNVs/indels and a moderate number of CNAs, including gain of 8q and 13q. d MSI/POLE mutated cell lines had a lower frequency of CNAs (vertical axis) along the genome than e MSS cell lines. In each plot, chromosomes are indicated on the horizontal axes and separated by vertical lines (whole and dashed lines for chromosomes and chromosome arms, respectively). Frequent aberrations are highlighted, including gains on 7p, 7q, 8q, 12p, 13q, 20q and losses on 4p, 4q, 17p, 18q and 22q, which are chromosome arms known to be frequently affected by CNAs in primary CRCs. CNA: copy number aberration, MSI/MSS: microsatellite instable/stable, POLE: POLE mutated, SNV: single nucleotide variant