Journal Article

DKFZ-2017-03906

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling.

Zuckermann, M. (First author)DKFZ* ; Hovestadt, V.DKFZ* ; Knobbe-Thomsen, C. B. ; Zapatka, M.DKFZ* ; Northcott, P. A.DKFZ* ; Schramm, K.DKFZ* ; Belic, J.DKFZ* ; Jones, D.DKFZ* ; Tschida, B. ; Moriarity, B. ; Largaespada, D. ; Roussel, M. F. ; Korshunov, A.DKFZ* ; Reifenberger, G.DKFZ* ; Pfister, S.DKFZ* ; Lichter, P.DKFZ* ; Kawauchi, D.DKFZ* ; Gronych, J. (Last author)DKFZ*

2015
Nature Publishing Group London

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/ncomms8391

Abstract: 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 has proven more challenging due to technical aspects. To provide a flexible and effective method for investigating somatic loss-of-function alterations and their influence on tumorigenesis, we have established CRISPR/Cas9-mediated somatic gene disruption, allowing for in vivo targeting of TSGs. Here we demonstrate the utility of this approach by deleting single (Ptch1) or multiple genes (Trp53, Pten, Nf1) in the mouse brain, resulting in the development of medulloblastoma and glioblastoma, respectively. Using whole-genome sequencing (WGS) we characterized the medulloblastoma-driving Ptch1 deletions in detail and show that no off-targets were detected in these tumours. This method provides a fast and convenient system for validating the emerging wealth of novel candidate tumour suppressor genes and the generation of faithful animal models of human cancer.

Keyword(s): Neurofibromin 1 ; PTCH protein, human ; Patched Receptors ; Patched-1 Receptor ; Ptch1 protein, mouse ; Receptors, Cell Surface ; Tumor Suppressor Protein p53 ; PTEN Phosphohydrolase ; Pten protein, mouse

---

Contributing Institute(s):

1. Molekulare Genetik (B060)
2. DKTK Essen (L401)
3. Pädiatrische Neuroonkologie (B062)
4. KKE Neuropathologie (G380)
5. DKTK Heidelberg (L101)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2015

---

Database coverage:
; ; ; BIOSIS Previews ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

---