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

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 Lailler, Andrea Sboner, Dong Gao, Devan A. Murphy, Zhen Cao, Shipra Shukla, Travis J. Hollmann, Lu Wang, Laetitia Borsu, Taha Merghoub, Gary K. Schwartz, Michael A. Postow, Charlotte E. Ariyan, James A. Fagin, Deyou Zheng, Marc Ladanyi, Klaus J. Busam, Michael F. Berger, Yu Chen () and Ping Chi ()
Additional contact information
Thomas Wiesner: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
William Lee: Computational Biology Program, 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
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
Ronak H. Shah: Human Oncology and Pathogenesis Program, 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
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
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
Charlotte E. Ariyan: Memorial Sloan Kettering Cancer Center
James A. Fagin: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Deyou Zheng: Albert Einstein College of Medicine
Marc Ladanyi: Human Oncology and Pathogenesis Program, 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
Yu Chen: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Ping Chi: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center

Nature, 2015, vol. 526, issue 7573, 453-457

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.

Date: 2015
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DOI: 10.1038/nature15258

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