Cancer-type-specific domain mutation landscapes across 21 cancer types | We identified ~ 100 cancer-type-specific significantly mutated domain instances (SMDs) in 21 cancer types (S2 Table; P-value = 10—7, Fisher’s Exact test , False Discovery Rate (FDR) <0.05). |
Cancer-type-specific domain mutation landscapes across 21 cancer types | Enrichment for Cancer Census genes was both strong and significant (~ 12-fold enrichment; P-value 2 5X 10—34, Fisher’s Exact test ), and suggests the remaining 54 genes that are not already known to be cancer drivers represent good candidates. |
Cancer-type-specific domain mutation landscapes across 21 cancer types | Of the 94 genes encoding cancer type-specific SMDs, 24 were found in the Sleeping Beauty dataset (~ 3-fold enrichment; P-Value 2 7X 10—06, Fisher’s Exact test ). |
Cancer-type-specific positioning of mutations within a given gene | These 52 genes were enriched for evidence of involvement in cancer, with 16 being Cancer Census genes (enrichment factor ~ 11.9; P-value = 6.7 X1043, Fisher’s Exact test), and 15 being candidate cancer genes according to the Sleeping Beauty screen (enrichment factor ~ 4.5; P-value = 1.9 X10'6, Fisher’s Exact test ). |
Cancer-type-specific significantly-mutated domain instance analyses | We analyzed the tendency of SMDs to co-occur in the same patient sample using Fisher’s Exact test (“stats” package in R). |
Cancer-type-specific significantly-mutated domain instance analyses | Overlap between our candidate gene set and Cancer Census genes and the Sleeping Beauty gene sets was also analyzed using the Fisher’s Exact Test (“stats” package in R). |
Cancer-type-specific significantly-mutated position based mutational hotspot analyses | We calculated the mutational hotspots within each domain instance encoded by a single gene based on Fisher’s Exact test with a P-Value cutoff 0.01 (FDR <0.05). |
Mutational trends of oncoproteins and tumor suppressor proteins | Functional sites were significantly overrepresented among oncogenic mutational hotspots (Odds ratio = 10.0, P = 0.0006, Fisher’s Exact Test ). |