| Title |
Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling
|
|---|---|
| Published in |
Nature Communications, June 2015
|
| DOI | 10.1038/ncomms8391 |
| Pubmed ID | |
| Authors |
Marc Zuckermann, Volker Hovestadt, Christiane B. Knobbe-Thomsen, Marc Zapatka, Paul A. Northcott, Kathrin Schramm, Jelena Belic, David T. W. Jones, Barbara Tschida, Branden Moriarity, David Largaespada, Martine F. Roussel, Andrey Korshunov, Guido Reifenberger, Stefan M. Pfister, Peter Lichter, Daisuke Kawauchi, Jan Gronych |
| 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. |
Login to access the Attention Digest and the Sentiment Analysis related to this output.
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 18% |
| Australia | 2 | 12% |
| United Kingdom | 1 | 6% |
| Italy | 1 | 6% |
| Unknown | 10 | 59% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 14 | 82% |
| Scientists | 3 | 18% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 2 | <1% |
| Peru | 1 | <1% |
| United Kingdom | 1 | <1% |
| Czechia | 1 | <1% |
| China | 1 | <1% |
| Canada | 1 | <1% |
| Unknown | 379 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 68 | 18% |
| Student > Ph. D. Student | 67 | 17% |
| Student > Master | 49 | 13% |
| Student > Bachelor | 31 | 8% |
| Student > Doctoral Student | 22 | 6% |
| Other | 43 | 11% |
| Unknown | 106 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 90 | 23% |
| Agricultural and Biological Sciences | 74 | 19% |
| Medicine and Dentistry | 24 | 6% |
| Neuroscience | 18 | 5% |
| Chemistry | 11 | 3% |
| Other | 50 | 13% |
| Unknown | 119 | 31% |