Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling.
作者： Marc Zuckermann , Volker Hovestadt , Christiane B. Knobbe-Thomsen , Marc Zapatka , Paul A. Northcott
DOI: 10.1038/NCOMMS8391
关键词:
摘要: In vivo functional investigation of oncogenes using somatic gene transfer has been successfully exploited to validate their role in tumorigenesis. For tumour suppressor genes this proven more challenging due technical aspects. To provide a flexible and effective method for investigating loss-of-function alterations influence on tumorigenesis, we have established CRISPR/Cas9-mediated disruption, allowing targeting TSGs. Here demonstrate the utility approach by deleting single (Ptch1) or multiple (Trp53, Pten, Nf1) mouse brain, resulting development medulloblastoma glioblastoma, respectively. Using whole-genome sequencing (WGS) characterized medulloblastoma-driving Ptch1 deletions detail show that no off-targets were detected these tumours. This provides fast convenient system validating emerging wealth novel candidate generation faithful animal models human cancer.
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