Extended Data Fig. 1. ID4 is distinct from small deletion signatures of known aetiology.

a, b, The mechanistic basis for many COSMIC indel signatures is unknown, with only 9 out of 18 having a proposed aetiology. ID2 (a) is attributed to DNA polymerase slippage^88,89 and ID6 (b) to microhomology mediated end-joining (MMEJ) activity, associated with HR deficiency^5,90. c, d, Mechanism for these signatures supported by: impaired MMR promoting replication slippage mutagenesis in MLH1^−/− colonic organoids resulting in ID2 (and ID1) signatures (c); ID6 contributing substantially (along with ID8) to the indel signature in ovarian cancer, in which HR deficiency is common (d). Analysis of data from⁹¹ in c; data for 73 ovarian adenocarcinomas with ID6 contribution from ICGC^5,50 in d.