Cell models with inducible oncogenic translocations allow to evaluate the potential of drugs to favor secondary translocations

Abstract

Dear Editor,Chromosomal translocations result from the interchange of genetic material between non-homologous chromosomes. Chromosomal translocations are formed by erroneous repair of double-stranded breaks (DSBs) via non-homologous end joining (NHEJ) [1]. Some genotoxic drugs produce DSBs and thus present a major risk factor for the development of oncogenic chromosomal translocations. The risk factors that interfere with translocationprone DSB repair, once DSBs are already formed, are obscure, and potential effects of drugs on translocation formation during this step have never been explored.The study of chromosomal translocations is complicated since naturally occurring translocations are rare, and the localization of breakpoints varies from kilobases to hundreds of kilobases, which complicates their detection. In contrast, when DSBs are generated at precise loci, the translocation can be easily detected by PCR. In the present work, we developed two experimental human B cell-based models to study lymphomagenic t(8;14) MYC-IGH and