TP53 and cancer: While alterations affecting TP53 and RAD51B were associated with increased genomic instability, alterations affecting the EGFR signaling pathway were associated with significantly lower levels of TMB (median p < 0.001) and, specifically PIK3CA with significantly lower levels of TBL in breast (BRCA, p < 0.00001), cervical (CESC, p < 0.01), colorectal (COADREAD, p < 0.01) and stomach (STAD, p < 0.00001) cancer (Figs. 4C, S21, and Tables S2 & 3).