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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Hong AL,Tseng YY,Cowley GS,Jonas O,Cheah JH,Kynnap BD,Doshi MB,Oh C,Meyer SC,Church AJ,Gill S,Bielski CM,Keskula P,Imamovic A,Howell S,Kryukov GV,Clemons PA,Tsherniak A,Vazquez F,Crompton BD,Shamji AF,Rodriguez-doi
10.1038/ncomms11987subject
Has Abstractpub_date
2016-06-22 00:00:00pages
11987issn
2041-1723pii
ncomms11987journal_volume
7pub_type
杂志文章abstract：:Low-light-level imaging techniques have application in many diverse fields, ranging from biological sciences to security. A high-quality digital camera based on a multi-megapixel array will typically record an image by collecting of order 10(5) photons per pixel, but by how much could this photon flux be reduced? In t...
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journal_title：Nature communications
pub_type： 杂志文章
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更新日期：2014-12-11 00:00:00
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