Figure 4: The 65 genes harboured loss-of-function mutations with strong cis-effects on the expression of these genes.

(a) The predicted cis-effect loss-of-function mutations across 12 tumour types (P(D)≥0.8 in at least one tumour type). (b) The histograms of posterior marginals of mutations and genes across tumour types. (c) The posterior marginals of mutations separated based on copy number status. (d) The loss-of-function mutations in the 65 cis-effect genes (all-cis), 30 novel predictions (novel cis), 23 cis-effect tumour suppressor genes (TSG-cis), 108 non-cis-effect TSGs (TSG-other) and 30 negative control genes (negative controls) segregated based on copy number status. (e) A ‘novel’ tumour suppressor gene AMOT is not significantly mutated based on frequency-based methods, but AMOT is enriched in loss-of-function mutations (tumour suppressor gene probability P(TSG)=0.92). (f) The loss-of-function mutations in STAG2 typically correlate with lower expression, except for a splice donor site mutation GT→GC mutation (both GT and GC are used by the splicing machinery). MuSiC SMG, significantly mutated genes predicted by MuSiC; TF, transcription factor; TSG probability, tumour suppressor gene probability.