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Activating mutations in ALK provide a therapeutic target in neuroblastoma

Author

Listed:
  • Rani E. George

    (Department of Pediatric Oncology,)

  • Takaomi Sanda

    (Department of Pediatric Oncology,)

  • Megan Hanna

    (and
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA)

  • Stefan Fröhling

    (Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • William Luther II

    (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
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA)

  • Stephan W. Morris

    (and)

  • Matthew Meyerson

    (and
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA)

  • A. Thomas Look

    (Department of Pediatric Oncology,)

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.

Suggested Citation

  • Rani E. George & Takaomi Sanda & Megan Hanna & Stefan Fröhling & William Luther II & Jianming Zhang & Yebin Ahn & Wenjun Zhou & Wendy B. London & Patrick McGrady & Liquan Xue & Sergey Zozulya & Vlad E, 2008. "Activating mutations in ALK provide a therapeutic target in neuroblastoma," Nature, Nature, vol. 455(7215), pages 975-978, October.
    • Handle: RePEc:nat:nature:v:455:y:2008:i:7215:d:10.1038_nature07397
    DOI: 10.1038/nature07397
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    Cited by:

    1. Esther R. Berko & Gabriela M. Witek & Smita Matkar & Zaritza O. Petrova & Megan A. Wu & Courtney M. Smith & Alex Daniels & Joshua Kalna & Annie Kennedy & Ivan Gostuski & Colleen Casey & Kateryna Kryts, 2023. "Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Karin Schmelz & Joern Toedling & Matt Huska & Maja C. Cwikla & Louisa-Marie Kruetzfeldt & Jutta Proba & Peter F. Ambros & Inge M. Ambros & Sengül Boral & Marco Lodrini & Celine Y. Chen & Martin Burker, 2021. "Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Cécile Thirant & Agathe Peltier & Simon Durand & Amira Kramdi & Caroline Louis-Brennetot & Cécile Pierre-Eugène & Margot Gautier & Ana Costa & Amandine Grelier & Sakina Zaïdi & Nadège Gruel & Irène Ji, 2023. "Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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