Berkeley Lab Life Scientists are Leaders in Team to Detect Cancer by Studying Proteins in the Blood

BERKELEY, CA — The National Cancer Institute (NCI) today announced awards totaling over $35.5 million to establish a network of teams that will investigate how to detect cancer by finding cancer-specific proteins and protein patterns in blood samples. The Department of Energy's Lawrence Berkeley National Laboratory is a leading member of the team based in the San Francisco Bay Area, in partnership with the University of California at San Francisco (UCSF), and the Buck Institute for Age Research.

The National Cancer Institute is investing in clinical proteomics technologies for cancer.

NCI, which is a part of the National Institutes of Health, calls the program Clinical Proteomic Assessment for Cancer (CPTAC). Leading the Bay Area team is UCSF's Susan J. Fisher, who is also a member of Berkeley Lab's Life Sciences Division. Joe W. Gray of Berkeley Lab and UCSF is a coprincipal investigator, as is Bradford W. Gibson of the Buck Institute; the University of British Columbia and the University of Texas's M. D. Anderson Cancer Center are also participating.

Principal investigator Fisher is a professor of cell and tissue biology at UCSF, Director of UCSF's Biomolecular Resource Center, a member of the UCSF Comprehensive Cancer Center, and a visiting staff scientist in Berkeley Lab's Life Sciences Division. Gray is Berkeley Lab's Associate Laboratory Director for Life and Environmental Sciences, Division Director of the Life Sciences Division, a professor of Laboratory Medicine at UCSF, and coleader of the breast oncology program at the Comprehensive Cancer Center. Gibson is a professor of chemistry and Director of the Chemistry Core at the Buck Institute.

Proteomics is the study of all the proteins in a cell, tissue, or organism, called its proteome, just as all of an organism's genes are called its genome. The goal of clinical proteomics for early detection of cancer is to identify certain proteins or patterns of proteins in bodily fluids, such as blood serum, which may signal cancer long before current methods of diagnosis reveal cancer in a patient.

"In some cancers, protein biomarkers have already been identified and can be tested for, as with PSA, the prostate specific antigen test, in prostate cancer," says Gray. "With this proteomics initiative the NCI would like to find a PSA-like test for all cancers, but better. Our approach will be to combine information from genome-wide studies of gene expression and gene processing with mass-spectrometry-based protein analysis technologies to identify cancer-specific proteins in the blood."

John Conboy of the Life Sciences Division has long studied one form of gene processing called alternative splicing, which will be a major part of the program that he will help direct. "Alternative splicing is a major mechanism for regulation of gene expression in humans, allowing a relatively small number of genes to encode many different forms of proteins," Conboy explains. "More than half of all the roughly 30,000 genes in the human genome are subject to alternative splicing."

During alternative splicing critical segments of a gene, called its exons, may be switched on or off, allowing the gene to produce variations in its protein products, as for example at different stages of a cell's development.

"We'll use special high-throughput microarrays to look for differences in the way tumor genes are spliced," says Conboy. "The purpose is to identify these aberrant splicing patterns at the exon level."

Once aberrant patterns of exons have been identified for key proteins associated with breast cancer, antibodies can be designed to seek out and tag these proteins in blood samples from patients.

"A vital part of this effort involves bioinformatics," Conboy says, the use of powerful computers and programs necessary to handle vast amounts of data. The insights gained from this research could also suggest therapeutic approaches to aberrant splicing in human cancer.

Says Gray, "Berkeley Lab's long support of research into fundamental processes like alternative splicing, and the access our researchers have to world-class facilities like NERSC" — DOE's National Energy Research Scientific Computing Center — "are excellent examples of the role the Department of Energy's national laboratories can play and the impact they can have in improving the management of cancer, in this case by enabling detection of cancer at a stage where it is more easily treated."

For more on the National Cancer Institute's Clinical Proteomic Technology Assessment for Cancer program, go to http://proteomics.cancer.gov.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our website at http://www.lbl.gov.