Activation of proto-oncogenes by disruption of chromosome neighborhoods

Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in…

• SO
  Sundhed og Sygdom, Det Frie Forskningsråd
• AS
  Austrian Science Fund

  Award: J3490
• NI
  National Institutes of Health

  Awards: NS088538, HG002668, CA109901, U01 DA 040588, AI120766, U54 DK107980, MH104610
• NH
  National Human Genome Research Institute

  Awards: R01 HG003143, U01 HG007910, U54 HG007010
• NC
  National Cancer Institute

  Award: U54 CA193419
• NI
  National Institute of General Medical Sciences

  Award: R01 GM 112720
• NI
  National Institute of Allergy and Infectious Diseases

  Award: U01 R01 AI 117839
• HH
  Hyundai Hope On Wheels