Fig. 3: Enrichment of somatic mutations in the 5′ UTRs of TP53 and ELF3.
From: Genome-wide mapping of somatic mutation rates uncovers drivers of cancer
a, Mutations from the PCAWG and Hartwig Medical Foundation cohorts observed within exon 1 of the 5′ UTR of the canonical TP53 transcript. DNA sequence from GRCh37 reference genome (+ strand). Mutation types, relevant sequence and regulatory elements as indicated in the legend. b–e, Analysis on PCAWG dataset (n = 2,279 samples). b, Distribution of indel sizes observed within 5′ UTRs of genes other than TP53 (n = 3,988 indels) and within the TP53 5′ UTR (n = 7 indels). P value comparing median indel lengths from one-sided Mann–Whitney U-test. c, Estimated mutation enrichment relative to the neutral mutation rate (observed / expected neutral mutations) within TP53 stratified by mutation type and location (number of mutations per category in Supplementary Table 17). Error bars, 95% CI. d, Distribution of mutations observed within donor and acceptor splice regions (defined as the 20 bp 3′ and 5′ of an exon, respectively) of the canonical TP53 transcript. Canonical splice SNVs and indels: mutations altering the two base pairs immediately adjacent to an exon boundary; splice region SNVs and indels: mutations intersecting the splice region but not the canonical splice sites. The donor splice region of exon 1 of the 5′ UTR (shown in a) is bolded. P value of observing the distribution of canonical and splice region mutations in the donor splice region of exon 1 5′ UTR compared to all other TP53 splice regions computed via a two-sided Fisher’s exact test. e, Expression of TP53 on standard deviation scale in carriers of TP53 5′ UTR mutations (n = 6) and non-carriers (n = 1,205), adjusted for tumor type and copy number in the PCAWG dataset (n = 2,279 samples). P value via one-sided Mann–Whitney U-test on adjusted and standardized expression values. Box plot elements are defined in Methods. f, SNVs overlapping ELF3 in the PCAWG and Hartwig Medical Foundation cohorts. Insets: zoom-in of the ELF3 5′ UTR region and estimated mutational enrichments with 95% CIs within this region (number of mutations per category in Supplementary Tables 17 and 18).
