A dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies

TP53, which encodes the tumor suppressor p53, is the most frequently mutated gene in human cancer. The selective pressures shaping its mutational spectrum, dominated by missense mutations, are enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated. We used CRISPR/Cas9 to ge...

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Udgivet i:Science
Main Authors: Boettcher, Steffen, Miller, Peter G., Sharma, Rohan, McConkey, Marie, Leventhal, Matthew, Krivtsov, Andrei V., Giacomelli, Andrew O., Wong, Waihay, Kim, Jesi, Chao, Sherry, Kurppa, Kari J., Yang, Xiaoping, Milenkowic, Kirsten, Piccioni, Federica, Root, David E., Rücker, Frank G., Flamand, Yael, Neuberg, Donna, Lindsley, R. Coleman, Jänne, Pasi A., Hahn, William C., Jacks, Tyler, Döhner, Hartmut, Armstrong, Scott A., Ebert, Benjamin L.
Format: Artigo
Sprog:Inglês
Udgivet: 2019
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Article
Online adgang:https://ncbi.nlm.nih.gov/pmc/articles/PMC7327437/
https://ncbi.nlm.nih.gov/pubmed/31395785
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1126/science.aax3649
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