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High-powered gene profiles provide clues to genes involved in common form of lung cancer

NSCLC cells, investigators scanned the cells with high-resolution cDNA (oligonucleotide) microarray equipment to find chromosome regions containing unusual numbers of gene copies. The technology, developed in conjunction with Agilent Technologies, was 50-100 times more powerful than had been used on NSCLC 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 gene deletions or over-copying had occurred.

Researchers re-analyzed the tumor and cell samples with the latest oligonucleotide expression microarray technology from Affymetrix, which indicates if individual genes are active. Using this data, they scanned the genes in these 93 regions to see if any were missing (and inactive) or present in unusually large amounts (and therefore highly active) in deleted or overcopied regions, respectively. This enabled them to narrow the search for genes that were the targets of the irregular regions. Intriguingly, all of the genes already known to be involved in NSCLC reside within the abnormal regions identified by the Dana-Farber team.

"This is compelling evidence that we're on the right track," says the study's other first author, Kwok-Kin Wong, MD, PhD, of Dana-Farber. "It's likely that the genetic mutations already linked to NSCLC 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."

As part of the study, investigators did microarray analyses on the two major subtypes of NSCLC, 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 possi
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Source:Dana-Farber Cancer Institute


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