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Researchers have identified a large variety of genetic alterations that appear to be responsible for the development and growth of squamous cell lung cancer, according to the results of a study published in Nature. The discovery could lead to new targeted agents designed to treat this type of cancer.

Lung cancer remains the leading cause of cancer death in the United States. Squamous cell lung cancer is a form of non-small cell lung cancer. Eighty percent of lung cancers are non-small cell lung cancers, and of these, about 30 percent are squamous cell. Squamous cell lung cancer develops in the large airways in the center of the lungs, whereas adenocarcinomas—the most common type of lung cancer—typically develop at the edges of the lungs. Squamous cell lung cancer occurs almost exclusively in smokers.

Advances in lung cancer treatment have allowed for more effective treatment of adenocarcinomas; however, these treatments are less effective in treating squamous cell lung cancer—which is why researchers continue to strive to identify the genetic components of the disease—and consequently, potential therapeutic targets for treating it.

Thus far, there has been no data compiled to characterize the genetic alterations in squamous cell lung cancer—and so there have been no targeted agents developed for its treatment.

Researchers from The Cancer Genome Atlas (TCGA) Research Network examined tissue samples from 178 patients with untreated squamous cell lung cancer. They compared tumor genes to the genes in normal tissue to ensure that a change in the tumor gene was the result of a mutation. They found a large number and variety of alterations, many of which appeared to affect pathways related to the development and growth of cancer. Genes that help repair cell damage were frequently altered.

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The researchers found complex genetic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumor. What’s more—they found statistically recurrent mutations in 11 genes, including a mutation of the TP53 gene in nearly all cancer specimens. They identified significantly altered pathways in NFE2L2, KEAP1, squamous differentiation genes, phosphatidylinositol-3-OH kinase pathway genes, CDKN2A, and RB1.

The findings are notable because they may enable scientists to develop targeted agents for squamous cell lung cancer.


The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. Published early online September 9, 2012. doi:10.1038/nature11404

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