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The Cancer Genome Atlas

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The Cancer Genome Atlas

In 2005, NCI and the National Human Genome Research Institute launched a pilot project to extend the genomics revolution to the field of cancer. The goal of this project was to identify the genetic changes that occur in specific types of cancer. The challenge was to sequence the full genomes of both malignant and normal tissues from hundreds of patients with each cancer type. Soon, The Cancer Genome Atlas (TCGA) project began to show that large-scale genome sequencing could yield unprecedented amounts of data on brain, lung, and ovarian cancers––and readily make the data available to the public and other researchers. To support TCGA, a national network of research and technology teams was established, and the early results spurred a decision to extend what became a priority project for NIH to include more than 20 additional cancer types. NCI-designated cancer centers are heavily involved in this effort.

TCGA grew from an NCI working group report co-authored by Dr. Leland Hartwell, then director of the Fred Hutchinson/University of Washington Cancer Consortium, and Dr. Eric Lander, a member of the extramural faculty of the David H. Koch Institute for Integrated Cancer Research at MIT. Lander was one of the leaders of the Human Genome Project and is also the founding director of the Broad Institute of Harvard and MIT and the director of its Genome Biology Program.

 

TCGA Science at the Cancer Centers

Much of TCGA’s infrastructure has grown up around NCI-designated cancer centers:

Translocation

Translocation

 

 

Collecting Biospecimens for TCGA

The collection of tissue and serum samples—known as biospecimens—from patients is a crucial step and a major challenge in genomic research, such as in TCGA. High-quality biospecimens are needed from as many as 500 patients for each cancer type, including specimens of both cancerous and normal tissue in quantities sufficient for use by all researchers in the TCGA network. The coordination of this effort is managed by the International Genomics Consortium in Phoenix, Arizona, and the Research Institute at the Nationwide Children’s Hospital in Columbus, Ohio, which is an affiliate of The Ohio State University Comprehensive Cancer Center.

Three NCI-designated cancer centers provided biospecimens as the pilot phase of TCGA got underway: lung cancer samples came from the Lung Cancer Tissue Bank of the Brigham and Women’s Hospital in Boston, part of the Dana-Farber/Harvard Cancer Center; brain cancer samples were sent from the University of Texas MD Anderson Cancer Center; and the ovarian cancer samples came from the Gynecologic Oncology Group at the Nationwide Children’s Hospital, which is affiliated with The Ohio State University Comprehensive Cancer Center.

 

Unlocking New Keys to Brain Cancer

TCGA illustrates the power of scientific collaboration as laboratories, specialized centers, and hundreds of researchers participate in the infrastructure that is established as each cancer is sequenced and studied. In addition to the formal project centers mentioned above, many experts in each type of cancer from cancer centers and other institutions have joined the TCGA Research Network. Their early results and TCGA data released to the wider research community provide important benchmarks for ad hoc groups of specialists pursuing publishable results for each cancer type.

The earliest findings from the pilot phase of TCGA were reported in the journal Nature on October 23, 2008. These findings were from the first large-scale, comprehensive study of glioblastoma multiforme (GBM), the most common type of brain cancer in adults. TCGA data revealed many significant gene mutations, including three that occur with substantial frequency that had not been detected previously. The researchers also identified core cell signaling pathways that are disrupted in GBM, and they were able to identify an unexpected potential mechanism that could explain how the body resists a chemotherapy drug that is commonly used in treating brain cancer. This group was led by investigators from the Dana-Farber/Harvard Cancer Center and included researchers from other NCI-designated cancer centers as well.

The results of a complementary study led by researchers from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University also revealed altered genes and pathways in GBM in genomic data that were published in Science in 2008. This research team included collaborators from several NCI-designated cancer centers, as well as private and international partners.

Together these two studies herald a revolution in glioblastoma care, where patients may receive treatments targeted at the activated pathways in their particular subtype of GBM.

 

Genomics – TCGA and Beyond

The TCGA Research Network has grown quickly and now includes more than 150 researchers at dozens of institutions across the country. The data produced by these investigators are rapidly made available to the entire research community through a public database.

Apart from TCGA, researchers at other NCI-designated cancer centers are pursuing genomic research as well. One such investigator, Dr. Timothy Ley of the Siteman Cancer Center at Washington University in St. Louis, and his colleagues have identified important mutations in a single gene that may account for the failure of treatment in a substantial number of patients with acute myeloid leukemia (AML). Originally discovered in the process of sequencing a single patient’s genomic DNA, the findings were validated in subsequent sequencing studies of the genomes of an additional 300 AML patients. These findings may be helpful in developing new drugs for patients resistant to standard chemotherapy. Further research is already underway.

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  • Posted: August 13, 2012