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Alternative transcription initiation leads to expression of a novel ALK isoform in cancer

Author

Listed:
  • Thomas Wiesner

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Medical University of Graz)

  • William Lee

    (Computational Biology Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Anna C. Obenauf

    (Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center)

  • Leili Ran

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Rajmohan Murali

    (Memorial Sloan Kettering Cancer Center
    Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center)

  • Qi Fan Zhang

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Elissa W. P. Wong

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Wenhuo Hu

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Sasinya N. Scott

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Ronak H. Shah

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Iñigo Landa

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Julia Button

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    †Present address: Johns Hopkins School of Medicine, Baltimore, Maryland 21205-2196, USA)

  • Nathalie Lailler

    (Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center)

  • Andrea Sboner

    (Weill Cornell Medical College/New York Presbyterian Hospital
    Institute for Computational Biomedicine, Weill Cornell Medical College/New York Presbyterian Hospital
    Institute for Precision Medicine, Weill Cornell Medical College/New York Presbyterian Hospital)

  • Dong Gao

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Devan A. Murphy

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Zhen Cao

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Shipra Shukla

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Travis J. Hollmann

    (Memorial Sloan Kettering Cancer Center)

  • Lu Wang

    (Memorial Sloan Kettering Cancer Center)

  • Laetitia Borsu

    (Memorial Sloan Kettering Cancer Center)

  • Taha Merghoub

    (Immunology Program, Memorial Sloan Kettering Cancer Center)

  • Gary K. Schwartz

    (Herbert Irving Comprehensive Cancer Center, Columbia University Cancer Center)

  • Michael A. Postow

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Charlotte E. Ariyan

    (Memorial Sloan Kettering Cancer Center)

  • James A. Fagin

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Deyou Zheng

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Marc Ladanyi

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Klaus J. Busam

    (Memorial Sloan Kettering Cancer Center)

  • Michael F. Berger

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center)

  • Yu Chen

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Ping Chi

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

Abstract

A novel ALK transcript expressed in a subset of human cancers, arising from a de novo alternative transcription initiation site within the ALK gene, is described; the ALK transcript encodes three protein isoforms that stimulate tumorigenesis in vivo in mouse models; resultant tumours are sensitive to treatments with ALK inhibitors, indicating a possible therapeutic avenue for patients expressing these isoforms.

Suggested Citation

  • Thomas Wiesner & William Lee & Anna C. Obenauf & Leili Ran & Rajmohan Murali & Qi Fan Zhang & Elissa W. P. Wong & Wenhuo Hu & Sasinya N. Scott & Ronak H. Shah & Iñigo Landa & Julia Button & Nathalie L, 2015. "Alternative transcription initiation leads to expression of a novel ALK isoform in cancer," Nature, Nature, vol. 526(7573), pages 453-457, October.
    • Handle: RePEc:nat:nature:v:526:y:2015:i:7573:d:10.1038_nature15258
    DOI: 10.1038/nature15258
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    Cited by:

    1. Julia Schöpf & Sebastian Uhrig & Christoph E. Heilig & Kwang-Seok Lee & Tatjana Walther & Alexander Carazzato & Anna Maria Dobberkau & Dieter Weichenhan & Christoph Plass & Mark Hartmann & Gaurav D. D, 2024. "Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Laia Simó-Riudalbas & Sandra Offner & Evarist Planet & Julien Duc & Laurence Abrami & Sagane Dind & Alexandre Coudray & Mairene Coto-Llerena & Caner Ercan & Salvatore Piscuoglio & Claus Lindbjerg Ande, 2022. "Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Zeyang Wang & Rui Fan & Angela Russo & Filippo M. Cernilogar & Alexander Nuber & Silvia Schirge & Irina Shcherbakova & Iva Dzhilyanova & Enes Ugur & Tobias Anton & Lisa Richter & Heinrich Leonhardt & , 2022. "Dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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