Research ArticleNeuroblastoma

Targeted Expression of Mutated ALK Induces Neuroblastoma in Transgenic Mice

Science Translational Medicine  04 Jul 2012:
Vol. 4, Issue 141, pp. 141ra91
DOI: 10.1126/scitranslmed.3003967

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Driving Neuroblastoma: A wALK in the Park

Correlation doesn’t prove causation. For example, even though you may always see your neighbors walking their dog right before you find that odiferous pile of unscooped pooh, unless you directly witness a walkaway or use DNA testing to trace the culprit, you can’t prove that they did it. Demonstrating causation is even more important in cancer biology—just finding a prevalent mutation in people with a particular type of cancer isn’t enough to show that mutation is actually relevant to disease. Heukamp et al. now address the potential causative role of anaplastic lymphoma kinase (ALK) mutations in neuroblastoma.

ALK mutations are found in most familial and some sporadic cases of neuroblastoma, a malignant tumor that affects children. To determine whether ALK mutations can drive the development of neuroblastoma, the authors introduced the most common ALK mutation into neural crest stem cells in mice. Tumors driven by this mutation resembled human neuroblastomas physiologically and mimicked the genetic structure of the disease. Mutated ALK and MYCN, another driver mutation for neuroblastoma, combined synergistically for tumor development. Heukamp et al. then used their new model to demonstrate that an ALK inhibitor currently in preclinical testing induced complete tumor regression in these mice; however, it remains to be seen whether these inhibitors will be useful in treating neuroblastoma in people.