Fig. 2

Map of TP53 mutations in patients and Mole-rats

We illustrate the mutational profile of TP53 using an in-house developed data visualisation tool built with Python to display somatic and germline mutations from cancer patients (https://tp53.isb-cgc.org/) [45] and germline data from rodent species [47, 48]. For the rodent data, two previous publications showed four different germline mutations or variants found in three different rodent species: S104N-Myospalax baileyi (M. b.), S104E-Microtus oeconomus (M. o.), R172K and R207K-Spalax judaei (S. j.) [47, 48]. In human, these TP53 variants correspond to S106N, S106E, R174K and R209K mutations, respectively. GRCh37/hg19 was used as our genome reference and NM_000546/NP_000537 as reference sequences for mutation annotations and protein domains. For the patient data, we included 4,299 samples from cases diagnosed with Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like Syndrome (LFL) (germline mutations) and 29,656 samples from general cancer patients (somatic mutations). We have filtered the database to only include samples with confirmed germline or somatic mutational status and with available genomic mutation annotation (GRCh37/hg19). The mutations are represented by discs at the codon position. The disc sizes and their distance from TP53 protein scheme are both proportional to the number of mutations. The most frequent alterations are annotated within each disc. The discs located above the protein scheme represent the somatic data for cancer patients, the ones immediately below refer to the germline mutations found in the LFS and LFL cases and the rodent data is displayed at the bottom of the plot. Mutations are coloured according to their effect (missense, frameshift-red, nonsense, silent, etc.) and TP53 protein structure is coloured highlighting its main domains (NP_000537). Even though, they are not frequent enough to be automatically highlighted (size of the discs and distance from TP53 protein scheme), we decided to display the ‘shared’ mutations between rodent and human cancer data for clarity purposes