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Updated: May 12, 2026

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts
Published on: January 8, 2017
Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations
Chengming Zhu1, Kevin D Mills, David O Ferguson
1Howard Hughes Medical Institute, The Children's Hospital and The Center for Blood Research, Boston MA 02115, USA.
Abstract:
Amplification of large genomic regions associated with complex translocations (complicons) is a basis for tumor progression and drug resistance. We show that pro-B lymphomas in mice deficient for both p53 and nonhomologous end-joining (NHEJ) contain complicons that coamplify c-myc (chromosome 15) and IgH (chromosome 12) sequences. While all carry a translocated (12;15) chromosome, coamplified sequences are located within a separate complicon that often involves a third chromosome. Complicon formation is initiated by recombination of RAG1/2-catalyzed IgH locus double-strand breaks with sequences downstream of c-myc, generating a dicentric (15;12) chromosome as an amplification intermediate. This recombination event employs a microhomology-based end-joining repair pathway, as opposed to classic NHEJ or homologous recombination. These findings suggest a general model for oncogenic complicon formation.
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