National Institutes of Health U.S. Department of Health and Human Services
"Toward a Comprehensive Genomic Analysis of Cancer"
NCI/NHGRI Workshop Questions and Answers
What is the status of efforts to characterize the human cancer genome?
The National Cancer Institute (NCI) and the National Human Genome Research
Institute (NHGRI) recognize the potential benefit that a comprehensive collection
of genetic and epigenetic alterations for major cancers could provide to the
NCI and NHGRI have agreed to examine the best approaches to achieve the goal
of building a comprehensive collection and analysis of mutations found in
human cancers. Through a multi-phase approach, NCI and NHGRI are examining
the major issues and barriers associated with compiling a complete catalog
of the genetic changes that characterize cancer.
Many biological, technological and scientific hurdles must be resolved in
order to attempt a large-scale project to accomplish this goal. To address
these issues, NCI and NHGRI sponsored a workshop in July 2005 to seek input
from members of the scientific community who have expertise in cancer and
clinical research, genomics, technology development, bioinformatics and bioethics,
as well as those who represent the public, non-profit, advocacy and private
sectors. Attendees were asked to provide guidance and expertise on a number
of issues, including the types of cancer that should be studied, optimal technology
strategies and bioethical issues. These discussions are important as NCI and
NHGRI develop plans for a pilot project.
How were these efforts conceived?
NCI and NHGRI began examining the feasibility of undertaking such a collaborative
program in a workshop held in April 2004 (See The Cancer Genome Anatomy Project (CGAP) [cgap.nci.nih.gov]). Later in
2004, the NCI's National Cancer Advisory Board (NCAB) convened a subcommittee
to examine the role of advanced technologies in addressing mission-critical
problems in cancer. This subcommittee, the Advanced Biomedical Technology
Working Group of the NCAB, presented its recommendations in February 2005
for the development of The Human Cancer Genome Project (Recommendation for a Human Cancer Genome Project ),
an ambitious program that would develop a comprehensive description of the
genetic basis of human cancer and, specifically, the complete identification
and characterization of genetic alterations present in a large number of major
types of cancer.
NCI initiated a collaboration with NHGRI to develop a pilot project to test
the feasibility of a large-scale effort to characterize all the genetic changes
that occur in cancer. Many experts believe that analysis of changes that occur
at the genetic level has the potential to provide valuable insights into the
causes of cancer. Epigenetic analysis also offers the potential to understand
how modifications of DNA molecules can turn genes on or off, without changing
the DNA sequence. The identification of these changes will lead to improved
means of diagnosing, treating and preventing cancer.
How will the characterization of the human cancer genome advance and
accelerate cancer research?
Fundamentally a genetic disease, cancer begins with one or more genetic alterations
within a single cell. As these alterations accumulate, the cell begins to
grow abnormally and can become malignant. Escaping the normal signals that
control cell growth, the mutated cells proliferate and can spread to other
parts of the body.
Scientists have identified many genes that are involved in human cancer. The
malfunctions of these genes occur by distinct mechanisms, and a systematic
characterization of these changes and their role in causing cancer could lead
to an increased understanding of the disease.
A comprehensive effort to examine changes in the cancer genome may offer an
effective way to identify all of the relevant genetic changes and malfunctions
that can contribute to cancer. The detailed analysis of the genomes in cancer
cells holds the promise to provide key information about many cellular pathways
involved in cancer. This new effort could provide researchers with specific
molecular targets for drug development. For example, Gleevec is a molecularly
targeted drug and has proven effective in the treatment of chronic myelogenous
leukemia, gastrointestinal stromal tumor and several other cancers.
How is this effort different from the Human Genome Project?
The Human Genome Project, an international project led in the United States
by NHGRI and the Department of Energy, was completed in April 2003 and provided
a reference DNA sequence of the human genome. The Human Genome Project also
helped to advance sequencing technologies, which continue to improve.
The proposed project will take advantage of these remarkable developments
to address cancer. Cancer is now understood to include more than 200 different
diseases, in which specific molecular transformations at the DNA level cause disruptions within intracellular pathways, spurring cells to grow uncontrollably. Because of the complexity of cancer, a comprehensive approach may hold the key to characterize fully the many genes in which molecular variations can occur.
Why are NCI and NHGRI pursuing the characterization of the human cancer
The Human Genome Project provided a model for approaching large-scale biomedical
research projects. The experience and technological advances resulting from
the Human Genome Project have made it feasible to consider large-scale science
projects. While conceptually feasible, a large-scale cancer genomic characterization
project will require new research into cancer biology, as well as additional
technological improvements. To demonstrate the practicality of this approach,
a pilot project will be a very important first step. The pilot project will
drive development of more cost-effective and efficient technologies that will
be needed to examine cancer genomes in sufficient detail.
Genomics, along with the development of advanced imaging methods, nanotechnology,
new drug discovery and development, improved biomarkers and proteins, and
extensive clinical research, potentially will change the way cancers are prevented,
diagnosed and treated.
How will the initial phases of this effort to characterize the human
cancer genome be structured?
The pilot phase of this effort will focus on addressing the wide range of
challenges in cancer biology and technology that must be met in order to implement
a successful large-scale human cancer genome project. The initial phases also
will analyze whether the comprehensive cataloguing of the sequence changes
in cancer will prove useful in understanding cancer and lead to new methods
of diagnosis and treatment.
A pilot program, which will determine the feasibility of a full-scale effort,
is scheduled to begin in fiscal year 2006. It is expected to take at least
three years to complete. The pilot project will be funded jointly by NCI and
NHGRI, and the management structure for the pilot will take advantage of the
scientific knowledge and management expertise of both institutes. In addition,
an external scientific committee of experts has been established to provide
guidance on all aspects of the design and evaluation of the pilot project.
The committee will work with NCI and NHGRI staff to evaluate progress and
revise scientific strategies, where necessary, to meet pilot project goals
How much will a pilot project cost and how will it be funded?
The pilot project is a major undertaking and will require considerable preparation
to address all of the technical and scientific issues. It also will establish
parameters that will demonstrate the feasibility of a large-scale project.
Although the recommendation proposed to the National Cancer Board in February
2005 included cost projections, NIH has not at this time determined
the exact cost of the pilot project. NCI and NHGRI have recently committed
to each contribute up to $50 million for the pilot, pending approval from
their respective scientific advisory boards and councils.
Will any other organizations be involved in these efforts?
NCI and NHGRI are actively seeking the involvement of partners from the public
and private sectors, as well as international collaborators.
What remains to be done between now and the start of the pilot project?
Based on input received from the scientific community during the July 2005
workshop, NCI and NHGRI have begun the planning phase of the pilot project.
Plans for a competitive approach to supporting the pilot project will be presented for approval by the National Cancer Advisory Board, NCI's Board of Scientific Advisors and the National
Advisory Council for Human Genome Research. A set of Requests for Applications
will be issued following the necessary institute approvals. The applications
will be evaluated by a rigorous peer-review process and then funded according
to standard NIH procedures.
Will the data generated by this effort be publicly available? How will
researchers access the data?
NCI and NHGRI will develop a data release policy that will continue the efforts
in the field of genomics to make data available as rapidly as possible to
the entire scientific community and public -- with little to no restrictions
on scientific use. The specific details of the data release policy will be
developed during the planning and implementation of the pilot project and
will be designed to achieve the joint goals of rapid public availability,
protection of privacy of patient information and appropriate use of intellectual
property to further the goal of widespread access to the benefits of this
research. These issues were discussed in greater detail during the July workshop.
Is this effort affiliated with other cancer projects, such as the Wellcome
Trust Sanger Institute's Cancer Genome Project in England?
NCI and NHGRI are reaching out to researchers and investigators to discuss
the successes and challenges of similar efforts around the world. NCI and
NHGRI program staff recently met with scientists from the Wellcome Trust Sanger
Institute and officials in the Wellcome Trust, as well as with the European
Commission, to discuss their current activities in sequencing and analyzing
cancer genomes. These discussions have provided valuable feedback to help
guide the direction of the NCI/NHGRI pilot project.
Where can I get more information?
A report from the July workshop is forthcoming.
For more information about cancer, visit the NCI Web site at www.cancer.gov
or call NCI's Cancer Information Service at 1-800-4CANCER (1-800-422-6237).
For more information on genomics and the Human Genome Project, visit the NHGRI
Web site at www.genome.gov.