With equipment designed to probe the smallest segments of the genetic code, researchers at Dana-Farber Cancer Institute and collaborating institutions have found something much larger: sections of the chromosomes of lung cancer cells where cancer-related genes may lurk.
In a study in the July 1 issue of the journal Cancer Research, the researchers used single nucleotide polymorphism (SNP) array technology, which focuses on the building blocks of individual genes, to identify regions of chromosomes where genes were either left out or multiplied over and over -- mistakes that are often associated with cancer. In this effort, SNP (pronounced "snip") arrays have been used to find gene-copy errors in lung cancer cells.
"In a previous study, we showed that SNP arrays offer a unique way of locating copy-number changes in cell chromosomes and of determining when genes on a pair of chromosomes are mismatched," says the study's senior author, Matthew Meyerson, MD, PhD, of Dana-Farber. "The current study demonstrates that high-resolution SNP technology is powerful enough to identify copy-number alterations that previously hadn't been found in lung cancer cells."
Working with 70 specimens of lung cancer tissue and 31 laboratory-grown lines of lung cancer cells, the investigators used high-resolution machinery to scan the cells' chromosomes in 115,000 locations. They found several areas that had already been identified as having copy-number errors, plus five new ones -- two where genes had been deleted, and three where they had been highly over-copied.
The next step will be to identify the specific genes involved in these alterations. That, in turn, could lead to new diagnostic tests and treatments for lung cancer, by far the most common form of cancer in the United States, and one of the most difficult to treat.
There is increasing evidence that therapies aimed at specific gene abnormalities can be effective in treating cancer. Last year, for example, Meyerson and colleagues demonstrated that the drug Iressa shrank tumors in patients with the most common form of lung cancer who carry an abnormality, or mutation, in a single gene.
Meyerson points out that the presence of copy-number changes doesn't guarantee that genes in the identified regions are involved in cancer. "We'll need to characterize the genes in these regions in detail to understand their role and whether they are cancer-causing or cancer-preventing genes," he remarks.
Co-authors of the study are Barbara Weir, PhD, Thomas LaFramboise, MD, Ming Lin, Rameen Beroukhim, MD, PhD, Levi Garraway, MD, PhD, Javad Beheshti, MD, Jeffrey Lee, Pasi Janne, MD, PhD, Cheng Li, PhD, and William Sellers, MD, of Dana-Farber; Katsuhiko Naoki, MD, PhD, of Yokohama Municipal Citizen's Hospital in Yokohama, Japan; William Richards, PhD, David Sugarbaker, MD, Fei Chen, and Mark Rubin, MD, of Brigham and Women's Hospital; Luc Girard, PhD, and John Minna, MD, of the University of Texas Southwestern Medical Center in Dallas; and David Christiani, MD, of the Harvard School of Public Health.
The study was funded in part by grants from the National Institutes of Health, the National Cancer Institute, the American Cancer Society, the Flight Attendant Medical Research Institute, and the Arthur and Rochelle Belfer Foundation.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
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