Activating mutations in ALK provide a therapeutic target in neuroblastoma

Rani E. George, Takaomi Sanda, Megan Hanna, Stefan Fröhling, William Luther, Jianming Zhang, Yebin Ahn, Wenjun Zhou, Wendy B. London, Patrick McGrady, Liquan Xue, Sergey Zozulya, Vlad E. Gregor, Thomas R. Webb, Nathanael S. Gray, D. Gary Gilliland, Lisa Diller, Heidi Greulich, Stephan W. Morris, Matthew Meyerson () and A. Thomas Look ()
Additional contact information
Rani E. George: Department of Pediatric Oncology,
Takaomi Sanda: Department of Pediatric Oncology,
Megan Hanna: and
Stefan Fröhling: Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
William Luther: Department of Pediatric Oncology,
Jianming Zhang: Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Yebin Ahn: Department of Pediatric Oncology,
Wenjun Zhou: Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Wendy B. London: Children’s Oncology Group Statistics and Data Center, University of Florida, Gainesville, Florida 32601, USA
Patrick McGrady: Children’s Oncology Group Statistics and Data Center, University of Florida, Gainesville, Florida 32601, USA
Liquan Xue: and
Sergey Zozulya: ChemBridge Research Laboratories Inc., San Diego, California 92127, USA
Vlad E. Gregor: ChemBridge Research Laboratories Inc., San Diego, California 92127, USA
Thomas R. Webb: St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA
Nathanael S. Gray: Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
D. Gary Gilliland: Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Lisa Diller: Department of Pediatric Oncology,
Heidi Greulich: and
Stephan W. Morris: and
Matthew Meyerson: and
A. Thomas Look: Department of Pediatric Oncology,

Nature, 2008, vol. 455, issue 7215, 975-978

Abstract: Neuroblastoma: a genetic link to ALK Neuroblastoma is the most common childhood cancer. There is a strong familial association and it was predicted over 30 years ago that there was a genetic element to the disease. Four groups now report the identification of mutations in the tyrosine kinase receptor ALK (anaplastic lymphoma kinase) in neuroblastoma patients. ALK acts as a neuroblastoma predisposition gene, and somatic point mutations occur in sporadic neuroblastoma cases. These mutations promote ALK's kinase activity and can transform cells and display tumorigenic activity in vivo. ALK inhibitors decrease neuroblastoma cell proliferation, so have potential as anticancer drugs.

Date: 2008
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DOI: 10.1038/nature07397

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