Integrated genetic and pharmacologic interrogation of rare cancers
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Integrated genetic.pdf
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Author(s)
Jonas, Oliver H.
Cheah, Jaime H
Langer, Robert S
Cima, Michael J.
Date Issued
June 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Hong, Andrew L. et al. “Integrated Genetic and Pharmacologic Interrogation of Rare Cancers.” Nature Communications 7 (2016): 11987. © 2016 Macmillan Publishers Limited
Version
Final published version
Abstract
Identifying therapeutic targets in rare cancers remains challenging due to the paucity of established models to perform preclinical studies. As a proof-of-concept, we developed a patient-derived cancer cell line, CLF-PED-015-T, from a paediatric patient with a rare undifferentiated sarcoma. Here, we confirm that this cell line recapitulates the histology and harbours the majority of the somatic genetic alterations found in a metastatic lesion isolated at first relapse. We then perform pooled CRISPR-Cas9 and RNAi loss-of-function screens and a small-molecule screen focused on druggable cancer targets. Integrating these three complementary and orthogonal methods, we identify CDK4 and XPO1 as potential
therapeutic targets in this cancer, which has no known alterations in these genes. These observations establish an approach that integrates new patient-derived models, functional genomics and chemical screens to facilitate the discovery of targets in rare cancers.
MIT Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
http://dx.doi.org/10.1038/ncomms11987
