biostudies-literatureZhang YHoward Hughes Medical InstituteNHGRI NIH HHSNCI NIH HHSNIGMS NIH HHS908-21https://www.ebi.ac.uk/biostudies/studies/S-EPMC3320767biostudies-literatureUnknown148(5)The extent to which the three-dimensional organization of the genome contributes to chromosomal translocations is an important question in cancer genomics. We generated a high-resolution Hi-C spatial organization map of the G1-arrested mouse pro-B cell genome and used high-throughput genome-wide translocation sequencing to map translocations from target DNA double-strand breaks (DSBs) within it. RAG endonuclease-cleaved antigen-receptor loci are dominant translocation partners for target DSBs regardless of genomic position, reflecting high-frequency DSBs at these loci and their colocalization in a fraction of cells. To directly assess spatial proximity contributions, we normalized genomic DSBs via ionizing radiation. Under these conditions, translocations were highly enriched in cis along CellSpatial organization of the mouse genome and its role in recurrent chromosomal translocations.PMC3320767R01 HG0031433P01CA092625-09S1P01 CA092625P01 CA092625-09F32 GM100617R01 HG003143-07Becker MSSimon ACMcCord RPHo YJHildebrand DGZhang YDekker JAlt FWLajoie BRfalseSpatial organization of the mouse genome and its role in recurrent chromosomal translocations.The extent to which the three-dimensional organization of the genome contributes to chromosomal translocations is an important question in cancer genomics. We generated a high-resolution Hi-C spatial organization map of the G1-arrested mouse pro-B cell genome and used high-throughput genome-wide translocation sequencing to map translocations from target DNA double-strand breaks (DSBs) within it. RAG endonuclease-cleaved antigen-receptor loci are dominant translocation partners for target DSBs regardless of genomic position, reflecting high-frequency DSBs at these loci and their colocalization in a fraction of cells. To directly assess spatial proximity contributions, we normalized genomic DSBs via ionizing radiation. Under these conditions, translocations were highly enriched in cis along 2012-01-01T00:00:00Z2012 Mar2025-04-04T21:05:48.984Z2019-03-27T00:52:00ZS-EPMC33207672234145610.1016/j.cell.2012.02.002