Complex oncogenic translocations with gene amplification are initiated by specific DNA breaks in lymphocytes

Sarah M. Wright, Yong H. Woo, Travis L. Alley, Bobbi Jo Shirley, Ellen C. Akeson, Kathy J. Snow, Sarah A. Maas, Rachel L. Elwell, Oded Foreman, Kevin D. Mills

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Chromosomal instability is a hallmark of many tumor types. Complex chromosomal rearrangements with associated gene amplification, known as complicons, characterize many hematologic and solid cancers. Whereas chromosomal aberrations, including complicons, are useful diagnostic and prognostic cancer markers, their molecular origins are not known. Although accumulating evidence has implicated DNA double-strand break repair in suppression of oncogenic genome instability, the genomic elements required for chromosome rearrangements, especially complex lesions, have not been elucidated. Using a mouse model of B-lineage lymphoma, characterized by complicon formation involving the immunoglobulin heavy chain (Igh) locus and the c-myc oncogene, we have now investigated the requirement for specific genomic segments as donors for complex rearrangements. We now show that specific DNA double-strand breaks, occurring within a narrow segment of Igh, are necessary to initiate complicon formation. By contrast, neither specific DNA breaks nor the powerful intronic enhancer Em are required for compliconin-dependent oncogenesis. This study is the first to delineate mechanisms of complex versus simple instability and the first to identify specific chromosomal elements required for complex chromosomal aberrations. These findings will illuminate genomic cancer susceptibility and risk factors.

Original languageEnglish (US)
Pages (from-to)4454-4460
Number of pages7
JournalCancer research
Issue number10
StatePublished - May 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Complex oncogenic translocations with gene amplification are initiated by specific DNA breaks in lymphocytes'. Together they form a unique fingerprint.

Cite this