"Genomic Loss and Gain and the Progression of Breast Cancer"
A hallmark of breast cancer development and progression is genomic instability, in particular gain and loss of genetic material. Genome-wide evaluations of amplification and loss of heterozygosity (LOH) events have identified dynamic regions in breast cancers that are likely to harbor oncogenes and tumor suppressor genes. The gain and loss events that promote progression of specific subtypes of breast cancer (based on genotype, steroid receptor status, or histological subtypes) are not known. In addition to the identification of the common patterns of gain and loss in breast tumor progression, a better understanding of the mechanism of amplification and LOH could ultimately lead to novel approaches for breast cancer detection or treatment.
I propose several aims to discover patterns of gain and loss in breast cancer and to evaluate DNA palindrome formation as a putative mechanism of these events.
(1) Determine whether palindrome formation is a common event in breast cancer in in vitro and in vivo systems.
(2) Examine the etiology of palindrome formation in breast cancer.
(3) Characterize early markers of genomic gain and loss in the context of breast cancer progression.