The researchers found that area contains a number of tumor suppressor genes including FUS1 that not only inhibited tumor growth and metastasis, but induced human lung cancer cell death.

Still, people who have lost one copy of their FUS1 gene at 3p21.3 have an active copy on their intact chromosome, but for reasons unknown as yet, the now-described defect in myristoylation occurs, rendering the proteins produced by the remaining FUS1 gene functionally inactive.

Inactivation of FUS1 appears to be a two-hit process, in which one good FUS1 gene is lost, and the other produces tumor suppressor protein that is disabled, says Ji.

The gene therapy trial underway at M. D. Anderson may offer a solution, says Roth. It uses bubbles of fat to encase millions of copies of FUS1 genes, which can be easily absorbed into tumor cells. So far, six patients with metastatic lung cancer have been treated.

Although replacement of the FUS1 gene in tumor cells does not specifically repair myristoylation defects, Roth says that experiments suggest overexpressing the gene somehow seems to overcomes this problem.

Replacing the FUS1 gene therapeutically at the earliest time possible in patients missing one copy of the 3p21.3 region may possibly prevent or delay the development of lung tumors, Ji says.

The study was funded primarily by grants from the National Cancer Institute and the National Institutes of Health. Other co-authors include John Minna, M.D., and Masashi Kondo, from UT Southwestern Medical Center, and from M. D. Anderson:  Futoshi Uno, M.D., Ph.D., Jiichiro Sasaki M.D., Ph.D., Masahiko Nishizaki M.D., Ph.D., Giovanni Carboni M.D., Kai Xu, and Edward Atkinson, Ph.D.

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