Reiterative CNA have been reported before in ALL22, 23 and the predominant mutational mechanism for these structural changes appears to be driven by the lymphoid recombinases RAG1/2.24 SNV in ALL have a different mutational mechanism involving APOBECs.24 It is unclear whether the predominance of CNA as recurrent changes in ALL is a reflection of the relative activity of these different mutational mechanisms, the prevalence of different selective pressures or differential functional impacts of CNA versus SNV on cellular fitness. Here, RAG1 is linked to acute lymphoblastic leukemia.