Grant: Project Grant - PA - Breast Cancer Prevention & Early Detection

Cancers are caused by mutations and genetic alterations. Conventional origins of mutations from chemicals in the environment or inherited mutations are known, but we have just begun to understand that some mutations that contribute to cancer originate from within our own cells. There are enzymes that exist in our cells that can alter the DNA sequence. Usually these enzymes act for our benefit and use their activity to alter the DNA sequence of viruses to make the viral DNA nonfunctional. However, sometimes when the levels of these enzymes are not kept in check, they can become too high and they can alter the DNA sequence or function of the human cell. If these mutations occur in genes that contribute to cellular replication, they can induce the formation or propagate maintenance of a cancer cell. Alternatively, the enzymes may act for our benefit and increase recognition and clearance of the tumor by the immune system, they may kill the cancer cell, or they may have a neutral effect. The enzymes can also interact with other cellular factors that promote or suppress cancer-type cell behavior. This research is focused on the internal origins of these mutations and cellular changes caused by a specific family of enzymes, called the APOBEC3 enzymes. If we can identify how their activity becomes unregulated and predict which outcome will occur in specific situations we can design therapies or use their presence as a prognostic tool for cancer.