Cancer scientists call for a large-scale human epigenome project

December 15, 2005

A vast code, invisible to the DNA sequencing effort that constituted the Human Genome Project, is rapidly being shown to play a direct role in human health. This "epigenome" - from the Greek epi, meaning "in addition to" - consists of chemical "amendments" that dangle like charms on a bracelet from the linear string of letters that spell out the genetic code.

Now, an international group of 40 leading cancer scientists says the time is ripe to undertake a large-scale international "Human Epigenome Project" designed to map the chemical modifications to DNA that comprise the epigenetic code. Their proposal, "A Blueprint for a Human Epigenome Project" -- published in the December 15, 2005 issue of Cancer Research -- summarizes the findings of an AACR-sponsored workshop held June 15-18, 2005, in Lansdowne, Va.

"Definition of the human epigenome and its application to developing diagnostic, prognostic and therapeutic tools will likely produce some of the earliest translational research benefits flowing from large-scale genome initiatives to the bedside," said Frank Rauscher, III, Ph.D., editor-in-chief of Cancer Research.

"It is time to create a concerted international effort to unlock the epigenomic information stored in our genome and use it for the benefit of human health," he added.

The new report spells out the needs, guidelines and expectations of a Human Epigenome Project (HEP), and describes the developing technologies that make the project currently feasible.

"One of the most exciting points to emerge from the meeting is that the technology needed for doing epigenetics on a high-throughput basis has advanced so far that people are already engaged in epigenomic studies on a piecemeal basis," said Peter A. Jones, Ph.D., D. Sc., president of the American Association for Cancer Research (AACR) and Director of the Norris Comprehensive Cancer Center at the University of Southern California. Jones and Robert Martienssen, Ph.D., a professor at Cold Spring Harbor Laboratory, New York, were co-organizers of the workshop.

"A coordinated, large-scale Human Epigenomic Project would pave the way for unforeseen breakthroughs in understanding normal and disease states," Jones added.

Epigenetic modifications to DNA exert profound influences on gene activity. For example, studies suggest that epigenetic variation may be responsible for subtle differences in appearance and behavior of identical twins, whose gene activity profiles at 3 years of age are nearly alike, but by age 50 diverge as much as unrelated individuals in the population at large.

Epigenetic aberrations also can play a role in normal and pathological processes, such as aging, mental health, and cancer, among others.

Several presenters at the workshop highlighted significant contributions that epigenetic phenomena make to a broad spectrum of human cancers. For example:Epigenetic modifications take several forms. The most intensively studied have been the addition of methyl groups, small "beads" of carbon and hydrogen, to DNA, which generally correlate with low gene activity. The histone proteins - molecular "clips" that hold the six feet of DNA tightly wound inside each cell - are modified by methylation, but also by the addition of chemical entities containing acetic acid, phosphorus, and a number of other species.

The complex nature of epigenetic modifications constitutes a challenge to the development of reliable, high-throughput methods of cataloging them. Several workshop participants, however, working in both industrial and academic settings, have developed techniques proving adept at tackling epigenetic complexity.

These include the so-called ChIP/chip methodology, in which intact chromatin - the complex of DNA and histones - is immunoprecipitated (brought out of solution using antibodies that recognize specific histone modifications) and analyzed on microarray "chips."

Modifications of DNA are also tracked on chips, following treatment with enzymes that recognize sites of methylation. Impressive accounts of success with these methods were presented at the workshop.

These accounts included a report from the European Epigenome Project, headquartered at the Wellcome Trust Sanger Institute in Cambridge, England, which has completed a pilot phase and expects to analyze 10 percent of the genome by fall 2006.

The proposed structure of a Human Epigenome Project takes into account that "there is not one epigenome," according to the authors, "but rather many different epigenomes." Epigenetic profiles differ among tissues, individuals and healthy vs. disease states. Workshop participants advocate choosing a small number of "reference" epigenomes to be analyzed at a high level of resolution. Tissues proposed for this analysis include peripheral blood cells and foreskin fibroblasts.

Participants agreed that a much larger group of samples could be examined using a lower resolution "scanning" approach that would help delineate basic principles of epigenetic effects on gene activity. The scanning approach would point out areas that should be "drilled down" with additional study.

As stated by the authors: "The goal of the HEP (Human Epigenomic Project) is to identify all the chemical changes and relationships... that provide function to the DNA code, which will allow a fuller understanding of normal development, aging, abnormal gene control in cancer and other diseases, as well as the role of the environment in human health."

Jones, Martienssen and the other workshop participants call for any U.S. effort to coordinate closely with those in other countries, including additional European projects underway as well as efforts in Japan, where an active epigenetic research community exists.

The workshop, sponsored by AACR, was also attended by representatives of the National Cancer Institute, which sponsored a related workshop on epigenomics in December 2004 and another one last month defining the epigenome.
-end-
Editors Note: To request a PDF copy of the Cancer Research article and editorial, please email: communications@aacr.org or call 215/440-9300, ext. 101.

Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract nearly 16,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.

American Association for Cancer Research

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.