Jeffrey Greenfield, MD, PhD

Jeffrey Greenfield, MD, PhD

By Jeffrey Greenfield, MD, PhD
Director, Children’s Brain Tumor Project

In the last issue of this newsletter, I told you about Dr. David Allis, my colleague across the street at Rockefeller University, and how his basic science research on histones had suddenly emerged as an important element in pediatric brain tumors. I’m thrilled to be working with Dr. Allis on this important research. As I write this issue, a brand-new paper by Peter Lewis has just been published confirming some of our best hopes.

Mechanism of Mutant Histone Protein in Childhood Brain Cancer RevealedDr. Lewis is a post-doc researcher who works with Dr. Allis, and he was intrigued by the research that linked the H3 histone mutation with the pediatric brain cancer called DIPG. That’s big news in itself, since histone mutations had never before been linked to a specific disease. But Dr. Lewis dug further into the data and made another remarkable finding. A single mutated amino acid on the histone can prevent the process of methylation — the process that “silences” the genes that may make cancer grow. Without that methylation there is no silencing, and without the silencing the gene becomes activated and a tumor can grow. As many as 17 percent of DIPG tumors may be caused by this one tiny aberration in one amino acid. When we find out how to turn methylation on in these cases, we just may have a new way to fight DIPG in those children with this mutation.

I’m thrilled by these findings, since they support my belief that the answer to these rare tumors lies in personalized medicine. If we know how to turn on methylation and we can identify those kids whose DIPG is caused by this mutation, we have hope for those children. When we discover the five or ten or more other reasons a tumor can grow, we can develop strategies specific to those tumors as well. Cancer is not one-size-fits-all, and the cures won’t be, either.

The findings were published in the April 1 issue of Science Daily. You can read the full article online at “Mechanism of Mutant Histone Protein in Childhood Brain Cancer Revealed.”