| http://purl.uniprot.org/citations/30124468 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30124468 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations underlie all cancers, and their identification and study are the foundation of cancer biology. We describe what we believe to be a novel approach to mutagenesis and cancer studies based on the DNA polymerase ε (POLE) ultramutator phenotype recently described in human cancers, in which a single amino acid substitution (most commonly P286R) in the proofreading domain results in error-prone DNA replication. We engineered a conditional PoleP286R allele in mice. PoleP286R/+ embryonic fibroblasts exhibited a striking mutator phenotype and immortalized more efficiently. PoleP286R/+ mice were born at Mendelian ratios but rapidly developed lethal cancers of diverse lineages, yielding the most cancer-prone monoallelic model described to date, to our knowledge. Comprehensive whole-genome sequencing analyses showed that the cancers were driven by high base substitution rates in the range of human cancers, overcoming a major limitation of previous murine cancer models. These data establish polymerase-mediated ultramutagenesis as an efficient in vivo approach for the generation of diverse animal cancer models that recapitulate the high mutational loads inherent to human cancers."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci122095"xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Alam M.M."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Lu C."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Zhang M."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Fu Y.X."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "You M.J."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Li H.D."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Akbay E.A."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Castrillon D.H."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/author | "Cuevas I."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/pages | "4179-4191"xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/title | "Polymerase-mediated ultramutagenesis in mice produces diverse cancers with high mutational load."xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://purl.uniprot.org/core/volume | "128"xsd:string |
| http://purl.uniprot.org/citations/30124468 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30124468 |
| http://purl.uniprot.org/citations/30124468 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30124468 |
| http://purl.uniprot.org/uniprot/#_E9QAP5-mappedCitation-30124468 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30124468 |
| http://purl.uniprot.org/uniprot/#_E9QAP6-mappedCitation-30124468 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30124468 |
| http://purl.uniprot.org/uniprot/#_Q3UR94-mappedCitation-30124468 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30124468 |
| http://purl.uniprot.org/uniprot/#_Q99LQ3-mappedCitation-30124468 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30124468 |
| http://purl.uniprot.org/uniprot/#_Q3TBY2-mappedCitation-30124468 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30124468 |