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Two New Lung Cancer Genes
By Adam Marcus

When chromosomes accumulate extra copies of genes, cancer often follows. This phenomenon, called DNA amplification, has been linked to tumors in several organs, including the brain, breast and lungs.

Using a novel way of scanning the genome, scientists have identified two new tumor genes in lung cancer cells that are amplified. The genes, called cIAP1 and cIAP2, each appear to block the normal ability of cells to self-destruct.

‘Even one duplicate gene can be deadly.’

The finding that extra copies of these genes are associated with lung cancer offers the possibility of measuring the genes in lung tumor samples, according to Christoph Plass, a cancer researcher at Ohio State University in Columbus, and leader of the study.

But first scientists must determine if the extra genes are linked to particularly aggressive tumors or poor prognosis. "Those question have not been addressed," say Plass, whose study appeared in Human Molecular Genetics.

The genes that Plass and colleagues identified are located on chromosome 11, and were present in tissue samples from small cell and non-small cell lung tumors, the two categories of lung cancer.

Earlier efforts to find amplified DNA in lung cancer have been successful, Plass says, but only at identifying chromosomes on which there were hundreds or thousands of extra copies of genes. Though much more time consuming, the new method can pick out as few as two or three extra copies. Even one duplicate gene can be deadly, he adds.

The researchers used a technique known as restriction landmark genome scanning in their work.

Joseph Costello, a cancer expert at the University of California, San Francisco, who uses the same technique to study brain tumors, says the new research "could turn out to be something important" for the treatment of lung cancer—"if follow-up studies show that these over-produced proteins contribute to" tumor growth.

DNA amplification is known to play a role in one form of breast cancer, in which patients make too much of a protein called HER2. Doctors treat these tumors with a drug that neutralizes the excess protein—and perhaps a similar approach could work with other cancers caused by amplified DNA, Costello says.

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Dai, Z. et al. A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes. Hum Mol Genet 12, 791-801 (April 1, 2003).

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