Triple negative breast cancers (TNBCs) comprise only a subset of all breast cancers, yet they are highly aggressive and offer the worst prognosis. A characteristic feature of TNBCs is their strikingly complex genomic profiles, highlighted by genomic rearrangements and chromosome structural aberrations. However, mechanisms responsible for the chromosomal alterations that potentially drive tumorigenesis remain unclear. We postulate that TNBCs depend upon the alternative, Lig4-independent NHEJ (A-NHEJ) pathway for DNA repair. We will use mouse models and human tumor samples to understand how progressive telomere dysfunction and activation of the A-NHEJ pathway generate pro-oncogenic chromosomal aberrations and the stepwise accumulation of mutational changes in favor of breast tumor initiation and progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA182280-01A1
Application #
8756430
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Pelroy, Richard
Project Start
2014-07-01
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Yale University
Department
Pathology
Type
Schools of Medicine
DUNS #
City
New Haven
State
CT
Country
United States
Zip Code
06510
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