Human Epigenome Project Could Help Cure Disease

Scientists push for a new effort to understand mechanisms that direct DNA

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By Steven Reinberg
HealthDay Reporter

THURSDAY, Dec. 15, 2005 (HealthDay News) -- Although the human genome was sequenced more than five years ago, it can provide scientists with comparatively few clues to the origins and treatment of disease.

The bulk of that information lies buried in the "epigenome" -- from the Greek epi, meaning "in addition to." The epigenome consists of chemical "amendments" to strings of DNA that spell out the human genetic code.

Now, an international group of 40 leading cancer scientists are proposing a new effort -- the Human Epigenome Project -- to map these chemical modifications.

They believe that a better understanding of the epigenome could move scientists closer to cures for cancer, Alzheimer's, and even aging.

"The whole of biology depends upon epigenetics," said study author Peter A. Jones, president of the American Association for Cancer Research and director of the Norris Comprehensive Cancer Center at the University of Southern California. "We don't know how the epigenome is organized. Knowing that will allow us to have new understanding of stem cell biology, the process of aging, the process of cancer development and more," he said.

The consortium of scientists outlined their proposal in the Dec. 15 issue of Cancer Research.

The epigenome stands at the intersection between the genome and the environment in the cell, Jones explained. It allows DNA to be packaged in such a way that gives it structure and function, he added.

Scientists need to understand how genes work in different cells. "It's time to get organized to understand the whole human epigenome," he said.

Understanding the epigenome has major implications for human disease, Jones said. "In cancer, these epigenetic changes shut down genes and switch them off so that they cannot be used, and this contributes to human cancer development," he said. "Most of those changes you cannot see if you just sequence DNA."

Mapping the epigenome is also important for developing new therapies, Jones noted. "There is a huge payoff in understanding how cancer is formed, how a cancer can be detected early, and how cancer can be treated," he said.

"Apart from that, these kinds of changes in your genome occur during the process of aging," Jones said. "Understanding the epigenome is critical to understanding aging."

In addition, many mental health problems appear to have an epigenetic component, Jones said. "The way the genes are organized can contribute to mental disease," he said.

Jones also noted that differences in stem cells are really differences in epigenetic states. "That's really what a stem cell is," he said.

"Embryonic stem cells have the potential to develop into a whole animal," Jones explained. But adult stem cells are "locked in" through epigenetic changes "in a way that they can only give rise to a particular type of cell," he said.

"If we are going to understand how to use stem cells, we are going to have to understand the human epigenome," Jones said. Sequencing DNA doesn't tell you how it works, Jones said. That's what mapping the epigenome will reveal, he believes.

A full understanding of the human epigenome will probably take a decade, Jones estimated. As of now, researchers have not even decided where to begin. "Every epigenome is different," Jones said. "We need to pick a few epigenomes to be sequenced in their entirety."

One expert thinks the human epigenome project will prove to be a much needed leap forward.

"Right now we have defined the hardware part of the genome," said Randy Jirtle, a professor of medicine at Duke University Medical Center. "The epigenome is, in effect, the 'software program' that runs the genome."

It is the epigenome that tells genes when to turn on and when to turn off, Jirtle said. "We cannot understand disease without that component," he said.

Jirtle believes the interaction between the early environment of an infant and his or her DNA is affected by the epigenome and establishes the potential for many diseases that develop later in life. "In order to understand how the disease process is working you have to understand the epigenome," he said. "You cannot understand disease without knowing this."

Robert A. Weinberg, a member of the Whitehead Institute for Biomedical Research, and a professor of biology at Massachusetts Institute of Technology, said, "The sequence information that has been generated by the human genome project has been a goldmine of information for many researchers in a variety of biomedical research areas. But that information is ultimately limited by the fact that we don't know when and where genes are expressed in various types of cells throughout the body, and what controls their expression."

"This epigenomics project holds the prospect of giving us, for the first time, an overview of the full repertoire of genes that are concomitantly expressed in a single human cell and how their expression is regulated. It's time has come," Weinberg said.

In addition to the Human Epigenome Project, the National Cancer Institute and the National Human Genome Research Institute announced that they are beginning an effort to speed up understanding of the molecular basis of cancer, according to a statement from the U.S. National Institutes of Health.

Called The Cancer Genome Atlas (TCGA), the project will first determine the feasibility of a full-scale effort to explore the universe of genomic changes that contribute to human cancers, according to published reports.

The groups have each committed $50 million over three years to the TCGA pilot project. The project will develop and test the science and technology needed to identify and characterize the genetic mutations and other genomic changes associated with malignancy.

The pilot project will involve several types of cancers chosen for their value in helping to determine the feasibility of a larger-scale project.

More information

For more on genomic research, visit the U.S. National Human Genome Research Institute.

SOURCES: Peter A. Jones, Ph.D., D. Sc., president, American Association for Cancer Research, and director, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles; Randy Jirtle, Ph.D., professor, medicine, Duke University Medical Center, Durham, N.C.; Robert A. Weinberg, Ph.D., Whitehead Institute for Biomedical Research, professor of biology, Massachusetts Institute of Technology, Cambridge, Mass.; Dec. 15, 2005, Cancer Research

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