NCI’s CGAP Seeks to Map Complete Genetics of Cancer

ALEXANDRIA, Virginia—Genetic alterations very early in the disease process lie at the root of every cancer. Functional genomics, the study of which genes are actually functioning at a given time or stage, affords a “new approach” to fighting cancer, reported Kristina Cole, MD, PhD, a cancer research training fellow at the National Cancer Institute, Bethesda, Maryland.

Addressing a plenary session of the 25th Annual Meeting of the Association of Community Cancer Centers (ACCC), she outlined the efforts of the Cancer Genome Anatomy Project (CGAP) to develop a detailed genetic picture of each step in the evolution of specific cancers in order to improve diagnosis, prevention, and treatment.

Multidisciplinary Project

The National Institutes of Health, the National Library of Medicine, pharmaceutical companies, and academic medical centers are all collaborating on this multidisciplinary project that seeks to discern the genetic anatomy of cancer cells over time and identify all the genes expressed in the normal progression of cancers.

Various technologies from biology and informatics are being used in combination to help build CGAP’s several cDNA genomic libraries, Dr. Cole said. These include human bulk tissue libraries and human microdissected libraries of lung, prostate, breast, ovary, and gastrointestinal cells.

Microdissection is a method that allows a user to go into tumor tissues, target specific cells of interest, and isolate and remove them for study. “Using laser capture microdissection, one can remove for microanalysis and photography only the particular cells desired,” she explained.

20,000 Genes Discovered

The goal of representing all genes expressed in a given cancer is proceeding rapidly, Dr. Cole said. “In prostate, for example, more than 40,000 sequences have already been read. Of the 60,000 human genes known (of a total of perhaps 100,000), CGAP has discovered 20,000,” she said.

All sequence information coming out of CGAP is publicly available, she noted, on the CGAP website located at www.ncbi.nlm.nih.gov/cgap/.

The construction of these on-line libraries also permits researchers to do “virtual data mining, the technique of searching computerized databases for significant relationships,” Dr. Cole said. Researchers, for example, can “mine” the CGAP libraries for candidate cancer genes.

Researchers can also link through the CGAP site to other databases concerned with genes and with gene mapping in-formation.

As an example of the power of these techniques, she described several applications to prostate cancer. CGAP has already found 7,677 genes expressed in prostate, with many others still unknown. “Sixty-five of these genes are differentially expressed in various cancer stages,” Dr. Cole said.

Some candidate genes implicated in the progression of prostate cancer have already been mapped. “So far, 143 genes specific to prostate and 328 genes unique to prostate have been identified,” she said. Some of these genes might provide good targets for either therapeutics or diagnostic agents.

Similar efforts in other organs can also produce useful results, she said, such as a potential marker for ovarian cancer analogous to PSA for prostate cancer.

Dr. Cole said that CGAP includes a number of other initiatives. The Cancer Chromosome Aberration Project (CCAP) is producing tools to characterize the distinct alterations in cancers. Molecular fingerprinting of various organs will produce 3D computer models of both the genomics and molecular organization of the cells, such as the “molecular prostate,” which is now in the process of construction.