• 2022-09
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  • 2021-03
  • 2020-08
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  • 2018-07


    Sequence data generated in this study has been deposited at the European Genome-Phenome Archive (
    with accession numbers:
    The most recent versions of our mapping and mutation calling pipelines, and supporting documentation, can be accessed from:
    Supplemental Figures
    Figure S1. Core Set of the Annotated Mutational Signatures, Related to Figures 1, 3, 5, and 6
    (A) The core set of the mutational signatures, including the Platinum set of the PCAWG signatures and SBS25 discovered in Hodgkin’s lymphoma cell lines. Signatures are displayed according to the alphabetical 96-substitution classification on horizontal axes, defined by the six color-coded substitution types and
    sequence context immediately 50 and 30 to the mutated Prostaglandin J2 axes (as per panel B). Vertical axes differ between individual signatures for visualization of their patterns (numerical patterns in Table S1) and indicate the percentage of mutations attributed to specific mutation types, adjusted to genome-wide trinucleotide frequencies. We thank PCAWG Mutational Signatures Working Group for the figure.
    (B) Transcriptional strand bias for SBS25. The mutational signature is displayed according to the 192-subsitution classification, incorporating the six substitution
    types in color-coded panels, the sequence context immediately 50 and 30 to the mutated base and whether the mutated base (in pyrimidine context) is on the transcribed (blue bars) or untranscribed (red bars) strand.
    Figure S2. Expression of Genes Previously Associated with Mutational Signatures in Examined Cancer Cell Lines, Related to Figures 3 and 4
    Each panel compares normalized basal expression of indicated genes, between the examined cell line (black) indicated on the top and cell lines from the 1,001 panel, from matching (blue) or other (beige) cell line classes as per their COSMIC classification (Table S2). P values (one-tailed; *p < 0.05, **p < 0.01, ***p < 0.001) correspond to the computed z-scores indicating the deviation of the mean expression of the gene in the examined cell line from the groups used in comparisons.
    (A) Expression of the mismatch repair genes in cell lines with MSI-associated signatures (SBS6, SBS14, SBS15, SBS20, SBS21, SBS26). Cell lines classified as high or low in microsatellite instability (Iorio et al., 2016) were excluded from the control panels.
    (B) Expression of UNG in cell lines with APOBEC-associated SBS2 and SBS13.
    (C) Expression of BRCA1 in cell lines with SBS3, associated with defective activity of the homologous-recombination-based double-strand break repair.
    A acquisition
    Mutations per genome
    Time period 1
    Time period 2
    Time period 3
    Stock cell lines Parent clones Daughter clones
    Translocations Tandem duplications Inversions Deletions
    Log (Fraction cytosine bases mutated per genome x10^7+1) 
    AGS A1b
    AGS B1a
    SiHa A1a
    SiHa A1b
    Sequence context
    Figure S3. Rearrangements and C>T Substitutions at NCG Contexts, Associated with SBS1 and 5-Methylcytosine Deamination, Are Generated over Time, Related to Figure 3
    Examination of additional mutation types acquired over time in cell line samples subjected to whole-genome sequencing and experimental design in Figure 2.
    (A) Bars indicate the numbers of color-coded rearrangement classes acquired during the time periods outlined in Figure 2, in indicated cell lines. Daughter clones
    were cultivated for the number of days indicated in brackets. z Only single parent clones from HT-115, LS-180 and AU565 cell lines were subject to whole-genome sequencing and their sequences were used as proxies for the mutational catalogs of the corresponding stock cell lines.
    (B) Each panel displays the fraction of the cytosine (or guanine) bases at 16 possible trinucleotide contexts that were mutated to thymines (or adenines, respectively) over the examined in vitro periods (Period 3; Figure 2), in 100 indicated daughter and granddaughter clones.
    (legend on next page)
    Figure S4. Episodic APOBEC Mutagenesis Is Likely Mediated by APOBEC3A, but It Does Not Depend on Proliferation Rates or Expression of APOBEC Genes in Examined Cell Lines, Related to Figures 3 and 4
    (A) Cell divisions were measured for 26 daughter and granddaughter clones from the indicated cell lines and compared to the genome-wide burdens of the indicated signatures acquired during the examined in vitro time frames (Period 3, Figure 2). The best fit, as well the adjusted R2, are indicated in plots where sufficient data points were generated for a statistical comparison. *p < 0.05.