Systematic, genome-wide scans of two types of cancer--breast cancer and colorectal cancer--have revealed important new findings about the genetic underpinnings of these diseases, a team of researchers at the Johns Hopkins Kimmel Cancer Center in Baltimore, Md., an NCI-designated Cancer Center, reports in the September 7 online issue of Science.* The Johns Hopkins group, which included Victor E. Velculescu, M.D., Ph.D., Ken Kinzler, Ph.D., and Bert Vogelstein, M.D., reports that by sequencing the protein-coding regions of some 13,000 genes within each of the tumors, they identified nearly 200 mutated genes, most of which were not previously known to play a role in cancer. Observed changes were not duplicated from one tumor type to the other, and the spectrum of mutations in the breast cancers was substantially different than in the colon cancers.
"The results from the genome-wide sequencing of only 11 breast tumors and 11 colon tumors at Johns Hopkins University are truly remarkable," said National Institutes of Health (NIH) Director Elias A. Zerhouni, M.D. "This groundbreaking work provides a dramatic proof of concept that this research approach holds great promise for providing an understanding of the genomic contributions to cancer. It also provides confirmation that the strategy selected for The Cancer Genome Atlas (TCGA) pilot project at the NIH is likely to produce important discoveries and impact cancer care."
TCGA was launched as a three-year, $100 million pilot project to determine whether large-scale genome sequencing and other genomic technologies could help researchers comprehensively identify the genetic changes that cause cancer. The pilot project, launched in December 2005, is a collaboration between the National Cancer Institute and the National Human Genome Research Institute.
"The findings at Johns Hopkins are just the beginning," said National Human Genome Research Institute Director Francis S. Collins, M.D., Ph.D. "As TCGA is launched and reaches full production, it will significantly and rapidly expand the amount and types of genetic information revealed about cancer. We anticipate that as TCGA scales up, we may be able to identify the majority of genetic changes that cause the most important and common forms of the major cancers. In fact, the large number of mutations reported in this paper offers a glimpse of what is yet to come and provides exciting new directions for drug discovery in breast and colon cancer."
"There are already a few excellent examples where the discovery of specific genetic changes has led to the development of effective, targeted treatments for cancer," said NCI Deputy Director Anna D. Barker, Ph.D. "Drugs such as Herceptin for breast cancer and Gleevec for chronic myelogenous leukemia and gastrointestinal stromal tumors have offered proof of concept that this is a high-value strategy. The report from the team at Johns Hopkins is very promising--both for TCGA and for this approach to drug discovery. Maximizing the numbers of targets available for drug development in a specific cancer means that patients will ultimately receive more personalized, less toxic therapies."
NIH will announce two major milestones in the development of The Cancer Genome Atlas pilot project in the next week.
*Sj÷blom T, Jones S, Wood, LD, Parsons DW, Lin J, Barber T, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JKV, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science Express, September 7, 2006. This study was funded, in part, by NCI and NHGRI.
For more details about The Cancer Genome Atlas, please go to http://cancergenome.nih.gov.
For more information about cancer, please visit the NCI Web site at http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Additional information about NHGRI can be found at its Web site, http://www.genome.gov.
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 http://www.nih.gov.
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