Kornelia Polyak, MD, PHD; Dana-Farber Cancer Institute; Idea Award:

The research that we had funded by the DoD is looking at the epigenetic alterations, particularly the DNA methylation patterns in human mammary epithelial stem cells and differentiated cells, because the idea was that the hypothesis we had that development and differentiation is an epigenetic program, and we thought that some of these genes that are differentiated and methylated between the stem cells and the more differentiated cells are potentially key regulators of this differentiation process in the stem cell function. And our preliminary data seems to support that because we found many transcription factors that are playing a role in stem cell functions that seem to be expressed only in the stem cells and they become methylated and shut off in the more differentiated cells. And we can show that if we re-express them that we can convert the cells to a more stem cell-like state. So that's very exciting.

In addition to looking at this DNA methylation patterns in the normal mammary gland, we looked at if those patterns are maintained in breast carcinomas, and indeed what we found that depending on the subtype of the tumors some of them seem to have the same differentiation pattern as the normal mammary epithelium has, but then others seem to be different. They have some kind of variant, differentiation. And many of these DNA methylation markers we can actually use to subtype the tumors depending on their differentiations status and also some of the DNA methylation markers only occur in a breast cancer cell with a particular phenyl type. And we are hoping that these markers could be used for prognostication of the patient and at the same time potentially used for diagnostics because they occur in a particular cell of a tumor that doesn't occur in a normal cell type. So that would be very interesting to explore in the future. What I like about the DoD meetings actually, which is unusual from some of the other scientific meetings, there are a lot of patients here and that always has some special influence on the interactions and the talks and some of the questions that are asked. Many of the consumers or non-scientists are very well educated. So they know a lot about breast cancer, they know a lot about treatment, and then most importantly they have a lot of personal stories to tell imparting their experiences and so many of their friends experiences. And that somehow can shift the balance in terms of what is the, you know like there is always a question about the clinical impact or how it's going to influence the patient.

We have very advanced technologies that we can tackle these problems and hopefully we can make real progress.