Fig. 1

Frequency of germline and somatic alterations in cancer-relevant pathways. a–b Circos plots displaying the individual-level frequency of alterations for each cancer type in DNA damage repair pathways (a) or oncogenes, tumor suppressors, and cancer predisposition genes (b). Individuals were grouped into four mutually exclusive categories based on the type of alterations observed in the gene set: Bi-allelic, combined germline and somatic alteration of the same gene; Mixed, germline and somatic alteration of different genes in the set; Germ: germline alterations only; and Som, somatic alterations only (mutation or methylation). The height of each bar represents the fraction of individuals in each alteration category. The black arrows highlight cancer types with bi-allelic mismatch repair alterations. Gene sets are ranked according to size moving clockwise. Pathway abbreviations and sizes: DR direct repair (N = 3 genes), TLS translesion synthesis (N = 19), MMR mismatch repair (N = 27), FA Fanconi anemia (N = 34), NHEJ non-homologous end joining (N = 37), BER base excision repair (N = 43), HR homologous recombination (N = 53), NER nucleotide excision repair (N = 70), OG oncogenes (N = 54), TS tumor suppressors (N = 71), and PRE predisposition genes (N = 144). There are a total of 382 unique genes, and gene sets are not mutually exclusive