The variations were found in a region of the ALK gene that controls enzymatic activity, according to Nature paper.

Investigators say that they found five mutations in the anaplastic lymphoma kinase (ALK) gene in 8% of the neuroblastoma tumor samples studied. A small molecule inhibitor caused the neuroblastoma cell lines carrying two of the mutations to die when treated in the laboratory, the researchers add.

The variations were found to reside in an area responsible for the enzymatic activity of the ALK receptor, which transmits growth and survival signals to the cell, according to the team. Also, some mutations gave neuroblastoma cells the ability to proliferate even without the molecules that normally activate the receptor in a highly controlled way.

To see whether such prolific growth can be stopped, investigators mixed an ALK-blocking molecule into batches of test cells with ALK receptors harboring each of the newly discovered mutations. The small molecule inhibitor TAE684 halted proliferation and brought on the death of cells with the most common mutation, designated F1174L, as well as cells with another mutation.

When investigators treated human neuroblastoma cells harboring the F1174L mutation with TAE684, the responses were just as dramatic as with the test cells. The results were confirmed when researchers used a second technique for shutting down ALK genes with the F1174L mutation.

Researchers at Dana-Farber Cancer Institute and other institutions collaborated on the study, which appears in the Oct. 16 issue of the Nature.

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