1. Phosphosite mutations in TP53 correlate with increased patient survival.
Phosphosite mutations in TP53 correlate with increased patient survival. (A) ActiveDriver analysis of TP53 pSNVs identifies a mosaic of nine phosphosite mutation hotspots (red columns) and deserts (blue columns) across multiple cancer types (top panel). Middle panel shows the protein sequence of TP53 with 29 phosphosites (black bars) and number of flanking phosphosites per residue (yellow and orange). Bottom panel shows number of SNVs per position, with the majority of mutations accumulating to the DNA‐binding domain in the central region of the sequence. Protein domains of TP53 are shown below the chart (TAD, transcriptional activation; PRO, proline‐rich region; NLS, nuclear localization signal; HO, homo‐oligomerization; C, C‐terminus). (B) Kaplan–Meier analysis of clinical data of ovarian cancer patients shows that TP53 pSNVs correlate with increased survival. Survival of patients with pSNVs (black solid line) is compared to survival of patients with other, non‐phosphorylation‐associated SNVs (red dashed line) as well as patients with wild‐type pSNVs (blue dashed line). (C) Long‐term survivors of glioblastoma with TP53 pSNVs (black solid line) show a similar correlation with increased survival; however, these observations have borderline statistical significance due to small sample size.
Jüri Reimand, and Gary D Bader Mol Syst Biol 2013;9:637
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