Gene clues give new insight into lung cancer
Published: June 28, 2005
Researchers have found new clues about the location of genes potentially involved in the most common type of lung cancer, which may suggest a range of possible targets for development of future therapies.
Using two forms of technology that make it possible to zoom in on smaller sections of cell chromosomes than ever before, researchers at Dana-Farber Cancer Institute led by Dr. Giovanni Tonon identified nearly 100 chromosome regions where genes are either over-copied or missing in non-small cell lung cancer.
“Previous studies have identified a small set of mutated, or abnormal, genes that are associated with non-small cell lung cancer,” Tonon said in a prepared statement. “But we also know that the chromosomes of these cells contain a large number of irregular regions –– where genes have either been deleted or copied over and over again –– which suggests that a large number of cancer genes remain to be discovered. The purpose of this study was to locate the likeliest candidates.”
The study will be reported in the Proceedings of the National Academy of Sciences online early edition (www.pnas.org/papbyrecent.shtml) this week.
Using tumor samples from 44 non-small cell lung cancer patients and 34 laboratory-grown lines of non-small cell lung cancer cells, investigators scanned the cells with a technology, called high-resolution cDNA (oligonucleotide) microarray. The technique allows researchers to find chromosome regions containing unusual numbers of gene copies.
The combined technologies used by the researchers were 50-100 times more powerful than had been used on these types of lung cancer cells in the past, enabling researchers to identify irregular sites more precisely. They found a total of 93 regions, each containing about 11 genes, where the genes were deleted or over-copied.
This enabled them to narrow the search for genes that were the targets of the irregular regions. Surprisingly, all of the genes already known to be involved in non-small cell lung cancer were located within the abnormal regions identified by the Dana-Farber team.
As part of the study, investigators also did microarray analyses on the two major subtypes of non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma, and found that their genomic profiles overlap in every area but one: squamous cell carcinomas contain an area of gene amplification, or over-copying, not found in adenocarcinomas.
Among the few genes in that area is one called p63, which is known to play a role in the ability of skin cells to reproduce. The new finding raises the possibility that adenocarcinoma and squamous cell carcinoma arise from an error in the same cell type and are driven to malignancy by similar genetic routes, the study authors say.
Finally, the researchers compared their data for non-small cell lung cancer (NSCLC) with similar data for pancreatic cancer, and found that both diseases have some chromosomal irregularities in common, suggesting that in both disorders, some of the same genes may be driving the tumors.
The study is part of a renewed effort by scientists worldwide to uncover the basic biology of lung cancer, the number one cause of cancer-related deaths in the United States. NSCLC accounts for about 75 percent of all lung cancers and is responsible for nearly 120,000 deaths in this country annually. It is one of the most difficult cancers to treat, with only 15 percent of patients surviving more than five years after diagnosis.
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What to Eat if You Have CancerIn recent years, technological advances have brought new precision to the search for gene abnormalities associated with cancer.
“This is compelling evidence that we’re on the right track,” says the study’s other first author, Dr. Kwok-Kin Wong of Dana-Farber. “It’s likely that the genetic mutations already linked to non-small cell lung cancer constitute only a portion of all the genetic errors that drive the disease. Our work provides a good starting point for scientists looking for others.”
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