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NCI to Expand TCGA to Up to 25 Tumor Types; Use Next-Gen Sequencing on Childhood Cancers

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Fueled by $1.3 billion in new funding from the American Recovery and Reinvestment Act, the National Cancer Institute plans to expand two cancer genome sequencing projects.

NCI Director John Niederhuber said at the American Association for Cancer Research meeting in Denver last week that the institute plans to expand the Cancer Genome Atlas project to 20 to 25 major tumor types.

In addition, the institute will apply next-generation sequencing to at least 100 tumor samples for each of several types of childhood cancers under the NCI's Therapeutically Applicable Research to Generate Effective Treatments, or TARGET, initiative.

TCGA, a collaborative project between the NCI and the National Human Genome Research Institute, kicked off in late 2005 with a three-year pilot project that was designed to explore the feasibility of a large-scale project and to develop new technologies. NCI and NHGRI each committed $50 million to the pilot, which included approximately $16.7 million in funding for the first year for genome sequencing centers.

In the fall of 2006, TCGA chose glioblastoma, lung cancer, and ovarian cancer as the first three cancer types to be studied, and funded three large-scale sequencing centers for the program: the Broad Institute, the Genome Center at Washington University, and the Human Genome Sequencing Center at Baylor College of Medicine. The project also chose seven institutions as Cancer Genome Characterization Centers, one Data Coordinating Center, and a Biospecimen Core Resource.

Last fall, the TCGA Research Network published its first results in Nature, an analysis of about 600 genes in almost 100 glioblastoma samples and matched normal tissue, sequenced by the traditional Sanger method (see In Sequence 9/9/2008)

At the time, David Wheeler, a scientist at Baylor and one of the study's authors, told In Sequence that the goal was to sequence 1,300 genes in total in 500 glioblastomas and controls, and that the network was planning to transition to next-generation sequencing platforms for the characterization of the lung and ovarian cancer samples.

In February, TCGA made molecular characterization data for ovarian cancer available on the NCI's website, and earlier this month, the TCGA network said it has selected more than 6,000 genes and miRNA targets for sequencing. "While not exhaustive, this list represents genes and sequences with a potential for being associated with human cancers based on published and unpublished research from the network," according to the website.

To date, TCGA has sequenced more than 200 glioblastoma samples, "along with lung and ovarian cancers," according to Niederhuber, and has identified genes in glioblastoma that were not previously associated with that cancer, as well as several subtypes. "With that foundation of success, we plan to move TCGA forward, with a goal of identifying all of the relevant genomic alterations in 20 to 25 major tumor types," he said.

During a separate AACR session last week, TCGA members said they expect to wrap up the pilot phase this fall, which involves characterizing 500 glioblastoma and ovarian cancer samples, and 200 lung cancers (see GenomeWeb Daily News 4/22/2009).

Under TARGET, the NCI is partnering with several other institutions to identify targets for several childhood cancers, initially focusing on high-risk acute lymphoblastic leukemia and neuroblastoma, according to the NCI's website.

For ALL, NCI is collaborating with the University of New Mexico Cancer Center, St. Jude Children's Research Hospital, and Children's Oncology Group. Collaborators for neuroblastoma are Children's Hospital of Philadelphia; the Center for Childhood Cancer's Biopathology Center in Columbus, Ohio; the Children's Hospital of Los Angeles; and the National Cancer Institute Center for Cancer Research.

Part of the project is to resequence genes that TARGET identifies by microarray expression analysis and whole-genome association scans, and sequencing of ALL-associated genes is conducted by Agencourt Bioscience under contract, according to the website.

Niederhuber said that TARGET begun last year and plans to "apply next-generation sequencing to at least 100 tumor specimens per childhood cancer."

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