The Cancer Genome Atlas
An update from Dr. Anna D. Barker, Deputy Director of the National Cancer Institute
The Cancer Genome Atlas (TCGA) is a collaborative initiative between the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) with a long-term goal of eventually “cataloging” all of the significant genetic changes in all cancers. It is being initiated as a three-year pilot project that will use the reference sequence and technologies from the Human Genome Project to gain a more comprehensive understanding of the changes in the three cancer types chosen for the pilot.
TCGA leverages NCI’s depth in cancer biology and genome characterization with the NHGRI’s high-throughput gene sequencing technologies. The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) are both part of the National Institutes of Health (NIH).
The overall goal of the TCGA Pilot Project is to increase our comprehensive understanding of the genetic basis of cancer, which has the potential to take time off of the clock and bring better therapies to patients faster. We anticipate that TCGA’s integrated database of molecular and clinical information will provide unprecedented opportunities for individual investigators to discover and develop a new generation of targeted diagnostics, therapies, and preventives for cancer.
I believe that TCGA is one of the most important scientific initiatives we will undertake early in this century to apply the results from the Human Genome Project to better understand the genetic and molecular basis of cancer and other diseases. The power of the output from this unprecedented project has the potential to change our understanding and management of cancer at ever step.
In September 2006, NCI announced that glioblastoma multiforme (brain cancer), lung, and ovarian would be the first three cancers studied in the TCGA Pilot Project. These three cancers collectively account for more than 210,000 cases of cancer each year in the United States.
Glioblastoma multiforme (GBM) was an important cancer for inclusion in this project — not only because brain cancer remains one of the most extraordinarily complex and lethal of all cancers, but because it also holds the potential to yield scientifically informative and enabling results. GBM also qualified for inclusion in the TCGA Pilot Project because the GBM biospecimen collections (donated by M. D. Anderson Cancer Center) met TCGA’s strict scientific, technical, and ethical requirements.
What makes GBM scientifically so interesting? GBMs appear to have a large number of genetic changes, likely the most of all astrocyte-based cancers. A recent sequencing study confirmed the presence of mutations in tyrosine kinase genes and other genes involved in cell signaling pathways, underscoring its genetic complexity and its potential to provide interesting data and new leads for investigators. It is believed that these abnormal genes play key roles in tumor growth and proliferation. In fact, there are already drugs in clinical testing for glioma that specifically target different abnormal molecules involved in proliferation pathways. GBM is also an ideal tumor to study on a practical basis, as it has few other cell types (in addition to cancer cells), such as stromal cells or inflammatory cells, that would contaminate or contribute extraneous non-tumor DNA in the extracted biomolecules being studied.
M. D. Anderson’s glioblastoma biorepository is managed and quality-assured by a leading neuropathologist and functions as a single high-quality source that has amassed extensive clinical and biological data associated with all of these samples. This level of sample quality is one of the key factors to maximizing the quality of the data that emerges from the pilot project. GBM was selected, in part, because it was one of the cancers for which there were at least 250 > 0.2 gram tissue samples (from patients participating in clinical trials) of the same cancer. This quantity helps ensure the statistical validity of the data that will be obtained. For each of the 250 GBM cancer samples, there were also matched “normal” tissues, such as blood from the same patient. These samples are critically important for comparison with tumor tissue. Additionally, each patient who provided a sample needed to give specific permission for their sample to be used in this testing.
The TCGA Pilot Project will involve collaboration and integration of several communities, such as the TCGA team of over 100 committed scientists, research and medical communities, and the patient community. The pilot project is also an excellent example of the increasing importance of patient involvement in two areas: tissue banking and clinical trials. The TCGA Pilot Project would not be possible without the collected high-quality tissue samples. In the future, cancer research will increasingly rely on patient awareness in these two critical areas.
It is our hope that the comprehensive genomic analysis, and the integration of sequence and clinical data, for GBM, lung, and ovarian cancer will identify new genes involved in these cancers. An extremely valuable outcome from the TCGA Pilot Project would be the ability to differentiate tumor subtypes based on genomic alterations. This level of understanding would allow clinicians to specifically select cancer patients for trials based on their tumor subtype, and maximize the patient’s opportunity to benefit from a specific therapy. We will establish a pre-competitive, publicly-available database of the various types of genomic characterization, genetic sequence, and clinical data and make it available as soon as possible to the scientific community.
Finally, although it is a “stretch” for the pilot project, our greatest hope would be to see this unparalleled integrated data set for GBM translated into positive clinical outcomes for patients.
Diagram provided by TCGA (NCI and NHGRI)