July 19, 2011

Biologists Identify New Gene That Drives Spread Of Lung Cancer

Cancer biologists at MIT have identified a new lung cancer gene that drives the spread of the deadly condition.

MIT reported that a major challenge for cancer biologists is determining which genetic mutations found in a cancer cell are most important for driving the cancer's spread.

The scientists used a new technique called whole-genome profiling to pinpoint the gene that drives progression of small cell lung cancer, which accounts for about 15 percent of lung cancer cases.

Alison Dooley, a recent PhD recipient in the lab of Tyler Jacks, director of MIT's David H. Koch Institute for Integrative Cancer Research, said the gene could lead to new drug targets.

Small cell lung cancer kills about 95 percent of patients within five years of diagnosis.  The researchers studied the disease's progression using a strain of mice.

"The mouse model recapitulates what is seen in human disease. It develops very aggressive lung tumors, which metastasize to sites where metastases are often seen in humans," such as the liver and adrenal glands, Dooley said in a statement.

This model allows scientists to follow the disease progression from beginning to end.

The researchers were able to identify sections of chromosomes that had been duplicated or deleted in mice with cancer by using whole-genome profiling.

The team found extra copies of a few short stretches of DNA, including a segment of chromosome 4 that turned out to include a single gene called Nuclear Factor I/B (NFIB).

The gene's exact function is still unknown, but it is involved in the development of lungs.

Researchers in Jack's lab collaborated with scientists in Matthew Meyerson's lab at the Dana-Farber Cancer Institute and the Broad Institute and found that NFIB is also amplified in human small cell lung tumors.

"The question, always, with mouse models is whether they can tell you anything about a human disease," Barry Nelkin, a professor of oncology at Johns Hopkins University School of Medicine, who was not involved in the research, said in a statement.

"Some tell you something, but in others, there may be only a similarity in behavior, and the genetic changes are nothing like what is seen in humans."

Researchers in Jacks' lab are now looking for the genes controlled by NFIB.

"If we find what genes NFIB is regulating, that could provide new targets for small cell lung cancer therapy," Dooley says.

Dooley and colleagues published their findings in the July 15 issue of Genes and Development.


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