Integrated genetic and pharmacologic interrogation of rare cancers.
Nat Commun
; 7: 11987, 2016 06 22.
Article
en En
| MEDLINE
| ID: mdl-27329820
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sarcoma
/
Receptores Citoplasmáticos y Nucleares
/
Carioferinas
/
Enfermedades Raras
/
Quinasa 4 Dependiente de la Ciclina
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos