In the News

NHGRI Funds Large-Scale Sequencing Centers

New Era of Sequencing for Cancer and Other Medical Purposes Begins

BETHESDA, Md., Mon., Nov. 20, 2006 – The National Human Genome Research Institute (NHGRI) today announced the results of the recent competition for support of its three large-scale sequencing centers, strengthening efforts to use the power of DNA sequencing to unlock the genomic secrets of human diseases. Also today, NHGRI and the National Cancer Institute (NCI), both part of the National Institutes of Health (NIH), announced that all three sequencing centers will devote a significant part of their efforts to The Cancer Genome Atlas (TCGA) Pilot Project, which is testing the feasibility of a large-scale, systematic approach to identify important genomic changes involved in cancer.

"Genomic sequencing has already made a substantial impact on both biological and medical research. A major focus of the next phase will be medical sequencing, which involves using sequencing technologies to identify genes that contribute to common human diseases, most of which have so far eluded gene hunters,” said NHGRI Director Francis S. Collins, M.D., Ph.D. “These discoveries will shed new light on the biological pathways involved in human health and disease, which in turn will lead to better strategies for diagnosis, treatment and prevention. It is gratifying that our sequencing centers are going to play a major role in bringing the promise of personalized health care closer to reality.”

The sequencing centers were selected through a competitive, peer-reviewed process based on scientific merit of each center’s application, as well as costs and efficiency. The three NHGRI-supported, large-scale sequencing centers, their principal investigators and their approximate Fiscal Year (FY) 2007 funding levels are:

• Broad Institute Sequencing Platform, The Eli & Edythe L. Broad Institute of the Massachusetts Institute of Technology and Harvard University; Eric S. Lander, Ph.D.; Cambridge, Mass.; $48 million.
• Washington University Genome Sequencing Center, Washington University School of Medicine, Saint Louis; Richard K. Wilson, Ph.D.; $41 million.
• Human Genome Sequencing Center, Baylor College of Medicine, Houston; Richard Gibbs, Ph.D.; $27.6 million.

The sequencing centers will be funded under cooperative agreements in which substantial programmatic involvement is anticipated among NHGRI and the recipients during performance of the scientific activities. The cooperative agreements also require each sequencing center to participate in the NHGRI’s Minority Action Plan by developing and implementing a training and education program to increase the number of under-represented minorities in genomic sciences.

Over the next four years, the centers in NHGRI’s Large-Scale Sequencing Research Network will utilize existing technology to continue large-scale sequencing of important targets. Almost half of the sequencing capacity will be dedicated to medical sequencing. The sequencing centers will also pursue new ways to increase the speed and lower the cost of DNA sequencing by testing and implementing several new technologies, which could potentially revolutionize large-scale sequencing and expand the use of genomics in medical research and health care. The combined sequence output from the centers, using current technologies, is expected to be about 12 billion DNA base pairs per month – the equivalent of four human genomes.

A significant portion of NHGRI’s medical sequencing program will be used for The Cancer Genome Atlas (TCGA), which was launched in December 2005 as a $100 million, collaborative three-year pilot project between NHGRI and NCI. TCGA consists of four integrated components: the Genome Sequencing Centers announced today, plus seven Cancer Genome Characterization Centers, a Data Collection Center, and the Biospecimen Core Resource. In the pilot phase of TCGA , the Genome Sequencing Centers will sequence a substantial number of selected gene targets to identify genomic changes, such as single base mutations and small insertion/deletions, in three types of tumors: brain (glioblastoma), lung (squamous cell), and ovarian.

“Cancer is an extremely complex disease. The Genome Sequencing Centers will play a pivotal role in our systematic effort to assess the range of genomic changes associated with malignancy,” said Mark S. Guyer, Ph.D., director of NHGRI's Division of Extramural Research. “This genomic information will provide the research community with a powerful tool for uncovering new therapeutic targets and developing better strategies for diagnosing, treating and preventing cancer.”

Other medical sequencing projects will use DNA sequencing to: discover new genes that are involved in common diseases; identify the genes responsible for dozens of relatively rare, single-gene (autosomal Mendelian) diseases; sequence all of the genes on the X chromosome from affected individuals to identify those involved in sex-linked diseases; and survey the range of variants in genes known to contribute to certain common diseases. The start of each project will depend on a number of factors, including the strategic selection of specific diseases and the availability of patient samples with appropriate informed consent.

“The availability of the human genome sequence, as well as other genomic resources produced by our sequencing centers, has transformed biomedical research everywhere,” said NHGRI’s Associate Director of Extramural Research Jane Peterson, Ph.D., who is also a program director for NHGRI’s Large-Scale Sequencing Research Network. “The addition of medical sequencing projects is challenging and quite exciting. Making these data publicly available to researchers will build upon the past success of NHGRI’s rapid data access model, and will continue to expand our knowledge of human health and disease.”

The sequencing centers also will focus increased attention on sequencing the genomes of organisms, such as bacteria, fungi, parasites and insects, which cause or transmit human diseases. In addition, they will pursue promising new areas of health-related research. For example, the large-scale sequencing program has already started to sequence the genomes of 100 microorganisms found in the human gut, and will build on this by using genomic sequencing to characterize the complex microbial communities found at many sites in and on the human body. Microbes have a profound effect on many human physiological processes, such as digestion and drug metabolism, and play a vital role in disease susceptibility. It is hoped new information about these organisms will lead to improved methods for monitoring and maintaining human health.

In addition to medical sequencing and technology development efforts, the sequencing research network will continue its groundbreaking work in comparative genomics, which involves sequencing and comparing the genomes of various organisms. This has proven to be one of the most powerful ways of identifying the parts of the human genome that are most functionally important, and therefore most likely to be relevant for an understanding of disease. In addition to the large-scale sequencing centers, other important comparative sequencing data will be contributed by the NIH Intramural Sequencing Center (NISC) in Rockville, Md. NISC conducts sequencing projects for NIH investigators and also generates sequence data to support various NHGRI sequencing program activities. NISC funding will be around $7 million, with half of this coming from intramural funds.

Since the completion of the human genome sequence in 2003, the sequencing centers have sequenced and published analyses of the genomes of a wide range of animals, including the mouse, chimpanzee, chicken, dog, rat, honey bee and sea urchin. This has provided researchers with a powerful tool for understanding the structure and function of the human genome. For instance, DNA sequences that are shared, or conserved, between humans and another species may be essential for turning genes on and off during development.

NHGRI's process for selecting sequencing targets to enter the pipeline for the sequencing centers begins with three working groups comprised of experts from across the research community. Each of the working groups is responsible for developing a proposal for a set of genomes to sequence that would advance knowledge in one of three important scientific areas: identifying areas in genetic research where the application of high-throughput sequencing resources would rapidly lead to significant medical advances; understanding of the human genome; and understanding the evolutionary biology of genomes.

A coordinating committee then reviews the working groups' proposals, helping to fine-tune the suggestions and integrate them into an overarching set of scientific priorities. The intent of the target selection process is to maintain flexibility so the focus of the sequencing program can be adjusted as the state of knowledge improves over the next four years in order to pursue the most biomedically compelling sequencing targets. The recommendations of the coordinating committee are reviewed and approved by the National Advisory Council for Human Genome Research, which in turn forwards its recommendations to NHGRI leadership. For more on the selection process, go to: www.genome.gov/11509736.

In addition, each sequencing center may use up to 10 percent of its capacity to work on targets of its own choosing. This will afford the sequencing centers some flexibility to demonstrate innovative uses of sequence information.

A complete list of organisms and their sequencing status can be viewed at www.genome.gov/10002154. High-resolution photos of many of the organisms being sequenced in NHGRI’s Large-Scale Sequencing Program are available at: www.genome.gov/10005141.

NHGRI is one of the 27 institutes and centers at the National Institutes of Health, an agency of the Department of Health and Human Services (DHHS). Additional information about NHGRI can be found at its Web site, www.genome.gov.

For more information about cancer and the National Cancer Institute, please visit the NCI Web site at www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

More information about The Cancer Genome Atlas Pilot Project is available at https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

National Institutes of Health to Map Genomic Changes of Lung, Brain, and Ovarian Cancers

The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health (NIH), today announced the first three cancers that will be studied in the pilot phase of The Cancer Genome Atlas (TCGA) project. The cancers to be studied in the TCGA Pilot Project are lung, brain (glioblastoma), and ovarian. These cancers, which collectively account for more than 210,000 cancer cases each year in the United States, were selected because of the availability of biospecimen collections that met TCGA’s strict scientific, technical, and ethical requirements.

“The selection of the first three cancer types to be studied by TCGA signals the scientific start of this initiative. Thanks to the tools and technologies developed by the Human Genome Project, scientists can collaborate to determine whether it will be possible to develop a useful atlas of the changes in the human genetic blueprint associated with all types of cancer,” said NIH Director Elias A. Zerhouni, M.D.

It is estimated that 174,470 new cases of lung cancer will be diagnosed in the United States in 2006. Lung cancer is the major cause of cancer-related mortality in both men and women, with an estimated 162,460 deaths expected to occur in 2006. Brain tumors account for nearly 90 percent of all primary central nervous system tumors. It is estimated that 18,820 new cases of brain cancer will be diagnosed in the United States this year, and 12,820 patients will die from the disease. Glioblastomas, also called glioblastoma multiforme or grade IV astrocytoma, are often fatal, malignant brain tumors that grow and spread very aggressively, and are the most frequently occurring type of brain cancer. An estimated 20,180 new cases of ovarian cancer and an estimated 15,310 deaths from the disease are expected in the United States in 2006. Often detected late, ovarian cancer causes more deaths than any other cancer of the female reproductive system.

NCI and NHGRI launched TCGA in December 2005 as a collaborative three-year pilot project to test the feasibility of using large-scale genome analysis technologies to determine all of the important genomic changes involved in cancer. When fully operational, TCGA will consist of four integrated components: a Biospecimen Core Resource (BCR); Cancer Genome Characterization Centers; Genome Sequencing Centers; and a Principal Bioinformatics Resource.

Today, the two institutes also announced the biorepositories that will provide biospecimens of the first three cancer types to be studied as part of the TCGA Pilot Project. The source of the lung cancer biospecimens will be the Lung Cancer Tissue Bank of the Cancer and Leukemia Group B (CALGB) clinical trials group, which is housed at the Brigham and Women’s Hospital in Boston, Mass. The source of the brain tumor (glioblastoma) biospecimens will be MD Anderson Cancer Center in Houston, Texas. The ovarian cancer biospecimens will be provided by the Gynecologic Oncology Group tissue bank at the Children’s Hospital of the Ohio State University in Columbus, Ohio.

NCI and NHGRI also announced today that the International Genomics Consortium, in collaboration with the Translational Genomics Research Institute, of Phoenix, Ariz., was selected to establish and manage TCGA’s BCR. The BCR will collect, store, process, and distribute biomolecules from cancerous and normal samples to the Cancer Genome Characterization Centers and Genome Sequencing Centers for genomic analysis.

TCGA’s Cancer Genome Characterization Centers will analyze samples from the BCR to identify key genomic alterations, such as copy number changes and/or chromosomal rearrangements, some of which are known to contribute to cancer development and/or progression. Selected genes will be sequenced by the Genome Sequencing Centers using high-throughput methods to identify small genomic changes, such as single base mutations and small insertion/deletions. TCGA Cancer Genome Characterization Centers and the Genome Sequencing Centers will be selected in the coming months.

“Cancer is exceedingly complex, and includes more than 200 different diseases. The overall goal of TCGA is to delve more deeply into the genetic origins that lead to this complexity, in order to enable the discovery and development of a new generation of therapies, diagnostics, and preventive strategies for all cancers,” noted Acting NCI Director John E. Niederhuber, M.D. “Results from the TCGA Pilot Project may provide the results we need to detect cancer early, in its most treatable stage, and provide new targets for the development of specific therapies.”

“The Cancer Genome Atlas will use cutting-edge technologies and knowledge from the Human Genome Project and other genomic studies to assess the range of genomic changes that cause the uncontrolled cell growth that characterizes cancer,” explained National Human Genome Research Institute Director Francis S. Collins, M.D., Ph.D. “TCGA will analyze hundreds of tumor specimens with multiple technologies, including the comparison of genome sequences from the cancers with the normal DNA sequence derived from the same patients, in order to identify changes that are specifically associated with cancer.”

The three cancers selected for study by TCGA were identified in a process that began in the fall of 2005 with a Request for Information (RFI) from NCI and notification to NCI Cancer Centers. The goal of the RFI was to identify candidate biospecimen collections that employed the highest level of ethical, technical, biologic, pathologic, and bioinformatics standards in the development of their biorepository.

The collections that qualified were evaluated in a three-stage process. The primary criteria addressed minimal requirements for the quality and quantity of the samples and the associated clinical information. Secondary criteria were then applied to effectively rank those tumor collections that met the primary criteria. Site visits to the biorepositories were then conducted by NCI and NHGRI staff. Critical factors for TCGA, such as timing, logistics, and the need for re-consent of patients, were factored into selection of the biorepositories to be considered. Finally, the biorepositories that emerged from this tiered process were further reviewed by an expert panel that included representatives from the surgery, research, pathology, bioethics, and patient advocate communities. The primary, secondary, and additional criteria are described in detail at http://cancergenome.nih.gov.

“The Cancer Genome Atlas Pilot Project is an important opportunity as we survey the potential future of cancer research. We must put aside our specific disease interests and channel our energy into the larger issues that can empower the cancer research enterprise to find new ways to improve outcomes for all cancer patients,” said Doug Ulman, cancer survivor, chief mission officer of the Lance Armstrong Foundation, and chair of the NCI Director’s Consumer Liaison Group.

Success factors for the TCGA Pilot Project include completion of genomic analysis of the three initial cancer types; identification of specific alterations in genes associated with cancer; and differentiation of cancer subtypes based on genomic changes. In addition, the pilot project will establish a publicly available integrated database that scientists can use to generate new knowledge through research. TCGA data will be made available through public databases supported by NCI’s cancer Biomedical Informatics Grid™ (caBIG™) and the National Library of Medicine’s National Center for Biotechnology Information (NCBI). TCGA data will be provided in a manner that meets the highest standards for protection and respect of the research participants.

“The Cancer Genome Atlas is a revolutionary project with the potential to provide cancer researchers the information needed to generate new hypotheses that can be tested in the laboratory and the clinic,” said NCI Deputy Director Anna D. Barker, Ph.D. “Achieving the long-term goal of TCGA to identify all of the significant genomic changes in all cancers will benefit patients by enabling the discovery and development of the molecular biomarkers needed to develop targeted interventions to prevent and cure cancer.”

Data from the TCGA Pilot Project will provide researchers and clinicians with an early glimpse of what promises to become an unprecedented, comprehensive “atlas” of molecular information describing the genomic changes in all types of cancer. TCGA will ultimately enable researchers throughout the world to analyze and employ the data to develop a new generation of targeted diagnostics, therapeutics, and preventives for all cancers, and pave the way for more personalized cancer medicine.

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NCI and NHGRI are two of the 27 institutes and centers at NIH, an agency of the U.S. Department of Health and Human Services.

For more details about The Cancer Genome Atlas, please go to http://cancergenome.nih.gov.

More information about lung, brain and ovarian cancers can be found athttps://www.cancer.gov/types/lung?redirect=true,https://www.cancer.gov/types/brain?redirect=true
and https://www.cancer.gov/types/ovarian?redirect=true, respectively.

For more information about cancer and the National Cancer Institute, please visit the NCI Web site at https://www.cancer.gov, or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

For more information about the National Human Genome Research Institute, please visit the NHGRI Web site at https://www.genome.gov.