Title

Activation of proto-oncogenes by disruption of chromosome neighborhoods

UMMS Affiliation

Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology

Date

3-3-2016

Document Type

Article

Disciplines

Biochemistry | Cancer Biology | Genetics and Genomics | Molecular Biology | Structural Biology | Systems Biology

Abstract

Oncogenes are activated through well-known chromosomal alterations, including gene fusion, translocation and focal amplification. Recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods led us to investigate whether proto-oncogenes occur within these structures and if 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 non-malignant cells was sufficient to activate proto-oncogenes. Mutations affecting chromosome neighborhood boundaries were found in many types of cancer. Thus, oncogene activation can occur via genetic alterations that disrupt insulated neighborhoods in malignant cells.

Rights and Permissions

Citation: Science. 2016 Mar 3. pii: aad9024. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Science (New York, N.Y.)

PubMed ID

26940867