Nature Communications (Feb 2019)
SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer
- Yibo Xue,
- Brian Meehan,
- Zheng Fu,
- Xue Qing D. Wang,
- Pierre Olivier Fiset,
- Ralf Rieker,
- Cameron Levins,
- Tim Kong,
- Xianbing Zhu,
- Geneviève Morin,
- Lashanda Skerritt,
- Esther Herpel,
- Sriram Venneti,
- Daniel Martinez,
- Alexander R. Judkins,
- Sungmi Jung,
- Sophie Camilleri-Broet,
- Anne V. Gonzalez,
- Marie-Christine Guiot,
- William W. Lockwood,
- Jonathan D. Spicer,
- Abbas Agaimy,
- William A. Pastor,
- Josée Dostie,
- Janusz Rak,
- William D. Foulkes,
- Sidong Huang
Affiliations
- Yibo Xue
- Department of Biochemistry, McGill University
- Brian Meehan
- Department of Pediatrics, McGill University, and Research Institute of McGill University Health Centre, Montreal Children’s Hospital
- Zheng Fu
- Department of Biochemistry, McGill University
- Xue Qing D. Wang
- Department of Biochemistry, McGill University
- Pierre Olivier Fiset
- Department of Pathology, Glen Site, McGill University Health Centre
- Ralf Rieker
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital
- Cameron Levins
- Department of Human Genetics, McGill University
- Tim Kong
- Department of Biochemistry, McGill University
- Xianbing Zhu
- Department of Biochemistry, McGill University
- Geneviève Morin
- Department of Biochemistry, McGill University
- Lashanda Skerritt
- Department of Biochemistry, McGill University
- Esther Herpel
- Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, and Institute of Pathology, Heidelberg University Hospital
- Sriram Venneti
- Pathology and Neuropathology, University of Michigan Medical School
- Daniel Martinez
- Children’s Hospital of Philadelphia Research Institute
- Alexander R. Judkins
- Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Keck School of Medicine of University of Southern California
- Sungmi Jung
- Department of Pathology, Glen Site, McGill University Health Centre
- Sophie Camilleri-Broet
- Department of Pathology, Glen Site, McGill University Health Centre
- Anne V. Gonzalez
- Division of Respiratory Medicine, Montreal Chest Institute, McGill University Health Centre
- Marie-Christine Guiot
- Department of Pathology, Montreal Neurological Hospital/Institute, McGill University Health Centre
- William W. Lockwood
- Department of Integrative Oncology, British Columbia Cancer Agency
- Jonathan D. Spicer
- Department of Surgery, McGill University Health Center
- Abbas Agaimy
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital
- William A. Pastor
- Department of Biochemistry, McGill University
- Josée Dostie
- Department of Biochemistry, McGill University
- Janusz Rak
- Department of Pediatrics, McGill University, and Research Institute of McGill University Health Centre, Montreal Children’s Hospital
- William D. Foulkes
- Department of Human Genetics, McGill University
- Sidong Huang
- Department of Biochemistry, McGill University
- DOI
- https://doi.org/10.1038/s41467-019-08380-1
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 13
Abstract
Non-small cell lung cancers with inactivating SMARCA4 mutations are currently undruggable. Here, the authors show that the absence of SMARCA4/2 reduces chromatin accessibility at the CCND1 locus, leading to a subsequent reduction in cyclin D1 expression, which promotes vulnerability of these cancers to CDK4/6 inhibition.
