Fig. 2: Overview of mutational patterns in all 41 CMMRD tumors sequenced.

Total TML in each tumor is reported, the ultrahypermutation ( >100mutations/Megabase(Mb)) and hypermutation ( >10mutations/Megabase(Mb)) thresholds are indicated by dashed lines. Tumor type, affected MMR gene and presence of somatic driver mutations in POLE or POLD1 are reported below. The contributions of COSMIC and de novo single base substitution (SBS) and indel mutational signatures indicated result from the signature extraction with MutationalPatterns. Mutational signatures are associated with various processes, SBS1 and SBS5: clock-like signatures, related to aging, SBS11: prior temozolomide treatment, SBS14: combined MMR and POLE deficiency, SBS15: MMR deficiency, SBS20: combined MMR and POLD1 deficiency, SBS26: MMR deficiency, ID1: aging and MMR deficiency, ID2: aging and MMR deficiency, ID12: unknown aetiology14, IDA-IDC: de novo extracted signatures. The cosine similarity between the original and reconstructed mutational profile is specified below the signature contributions. Tumors are identified by the individual ID, followed by tumor type (B=brain, G = gastrointestinal (GI), H=hematological), treatment-status (N= treatment-naïve, A= after treatment), tumor status (P=primary tumor, M=metastasis or relapse) and the order in which they occurred (Fig. 1 and Table S2). *In C04-BNP01, a somatic POLD1 mutation was validated in transcriptomic data only. Source data are provided as a Source Data file.