Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations
Philipps University of Marburg · Goethe University Frankfurt · +10 more institutions
Abstract
The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells. This high-resolution approach, covering 94.5% of all cancer-associated TP53 missense mutations, precisely mapped the impact of individual mutations on tumor cell fitness, surpassing previous deep mutational scan studies in distinguishing benign from pathogenic…
Citation impact
- FWCI
- 41.29
- Percentile
- 100%
- References
- 105
Authors
25Topics & keywords
- Biology
- Missense mutation
- Genetics
- Nonsense mutation
- CRISPR
- Genome editing
- Mutation
- Computational biology
- Good health and well-being
Funding
- VVon-Behring-Röntgen-StiftungAwards: 65-0004, 66-LV06, 71-0012
- DFDeutsche ForschungsgemeinschaftAwards: STI 182/15-1, GRK2573, CRC1213 A10N, 109546710 Project A10, SA 1923/7-1, STI 182/13-1, JO 1473/1-3
- BFBundesministerium für Bildung und ForschungAward: 031L0063
- HMHessisches Ministerium für Wissenschaft und Kunst
- JCJosé Carreras Leukämie-StiftungAward: 09 R/2018
- DKDeutsche Krebshilfe