Cancer and DNA: Imbalance in genetic controller may be key to cancer
If DNA contains the code of life, epigenetics is the code on top of the code. It works through small molecular “control knobs” called methyl groups placed either directly on the DNA or on closely linked proteins. These methyl groups control the activity of genes, turning some on and others off.
Certain genes, however, fall into a special category. These “bivalent” genes can be both turned on and turned off depending on what part of them is methylated. So they find a balance, neither fully active nor completely shut down, but perfectly poised and controlled epigenetically.
Researchers led by City of Hope's Gerd Pfeifer, Ph.D., the Lester M. and Irene C. Finkelstein Chair in Biology, recently pinpointed a key molecular change in cells that can inadvertently tip the genetic balance in favor of cancer. The findings may be the first to use human tissue samples to positively link an epigenetic code to the development and spread of colon cancer.
Pfeifer, who is a professor in the Department of Cancer Biology, along with Maria Hahn, Ph.D., a staff scientist in the department, Arthur Li, a biostatistician in the Department of Research Information Sciences, and their collaborators studied tissue samples from colorectal cancer patients, looking at bivalent genes that were associated with cancer. They suspected that the epigenetic balance for these genes had been tipped — and they were right.
Several of these cancer-promoting genes had been pushed into a state of being highly activated. Running out of control, the genes pushed cells to become malignant and even to spread.
“It’s not understood what causes the bivalent genes to tip into the fully activated state,” said Pfeifer. “Once active, however, the runaway genes allow cancer cells to thrive.”
As their research continues, the scientists hope to understand the mechanism that causes the epigenetic imbalance. Knowing that could one day lead to therapies to stabilize the bivalent genes or eliminate cells that fall out of balance.
Research reported in this publication was supported by the National Institutes of Health under grant number R01-CA-084469-14. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Learn more about Gerd Pfeifer's research into DNA methylation and cancer at City of Hope.