By Edward R. Winstead

October 6, 2009

During a visit to NIH on Wednesday, September 30, President Barack Obama toured a laboratory with (from left to right) Secretary of Health and Human Services Kathleen Sebelius, National Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci, and NIH Director Dr. Francis Collins.

During a visit to the NIH campus last week, President Barack Obama announced that NIH will spend $275 million over the next 2 years to catalogue the genetic changes driving more than 20 types of cancer.

The grant, which includes $175 million in Recovery Act funds, will support the second phase of The Cancer Genome Atls(TCGA) project. This collaborative effort led by NCI and the National Human Genome Research Institute (NHGRI) aims to discover the molecular alterations that occur in major types and subtypes of cancer.

Leaders of the project said that the TCGA pilot study, launched in 2006, has demonstrated the feasibility of using integrated genomic strategies to characterize the molecular alterations in cancer. The first three cancers profiled were brain, lung, and ovarian.

"The pilot project showed not only that we could build the infrastructure for a large-scale genome mapping project, but also that a very large team of scientists could come together and do work that benefits the entire community," said NCI Deputy Director Dr. Anna Barker, who co-leads the research program.

More than 150 researchers at some 18 centers around the country will use various genomic technologies, including next-generation DNA sequencing machines, to produce the data. As has happened during the pilot project, the information will be deposited in public databases, where the scientific community can use the results for many purposes, including searching for vulnerabilities in tumors that could be exploited by therapies.

The project aims to complete in-depth genomic analyses of 10 cancer types using approximately 500 samples of both tumor and matched normal tissue of each type, while also sequencing and characterizing at least 100 tumors for each of the additional cancers in the next 2 years, officials said.

The TCGA research network will broaden its mapping efforts and generate more in-depth analyses of all of the cancers in the following 3 years. Dr. Barker noted that the development of new bioinformatic tools to analyze large amounts of genomic data will be critical to the project's success.

NCI and NHGRI will each commit $50 million in non-Recovery Act funds to TCGA over the initial 2-year period. The two institutes have also committed to funding the remaining 3 years of the project, and the details will be finalized shortly, officials said.

The 20 cancer types have not been announced, but the criteria include relatively high incidence, substantial lethality, and the availability of high-quality biological samples for analysis. A type of kidney cancer called clear cell renal cell carcinoma and a type of breast cancer called invasive ductal carcinoma are examples of cancers likely to be priorities.

"This ambitious effort promises to open new windows into the biology of all cancers, transform approaches to cancer research, and raise the curtain on a more personalized era of cancer care," NIH Director Dr. Francis Collins said in a news release.

For example, TCGA data could accelerate the discovery of biological markers associated with specific subtypes of cancer. Even before new drugs or diagnostic tools are developed for patients with these subtypes, physicians could use biomarkers to assign patients to the most appropriate clinical trials, Dr. Barker noted.

The project also collects detailed information about each participant's clinical course and outcomes, so researchers can identify associations between genomic changes and treatment responses. For example, TCGA investigators reported recently that certain genetic alterations in patients with glioblastoma (a form of brain cancer) are associated with the development of resistance to a drug that is commonly used to treat the disease.

In his speech at the NIH Clinical Center on September 30, President Obama announced that $5 billion in 2009 Recovery Act funding for NIH would support more than 12,000 grants. Calling the Recovery Act grants the "single largest boost to biomedical research in history," he said that the investment would drive cutting-edge research across America, unlocking treatments to diseases such as cancer "that have long plagued humanity."

After attending a scientific meeting on brain cancer last week, Dr. Barker said that TCGA was already making a difference in the field. Many presentations included TCGA data, and clinicians were discussing the issue of drug resistance uncovered by project investigators. Some researchers at the meeting had begun to work on glioblastoma largely because reliable genomic data on the tumor type were available, she noted.

"This project has transformed our view of glioblastoma, first and foremost, by providing new therapeutic points of attack," Dr. Ronald DePinho of the Dana-Farber Cancer Institute, who was also at the meeting, said in an email message. "It is an extraordinary resource for all of cancer science, not just glioblastoma."

"What is particularly helpful for the field," he continued, "is that investigators can now conduct a comprehensive analysis of pathways and their interactions across all dimensions of the genome space–RNA, splicing, microRNA, copy number, mutations, and epigenetics."

As the project's next phase gets under way, Dr. Barker predicted that the scientific community would continue to use the data to develop new insights into the biology of cancer.

"I think the TCGA approach has enormous promise to change the face of cancer research as we roll out the genomic profiles on these various tumors in the next 5 years," she said.

This article originally appeared in the NCI Cancer Bulletin.