| http://purl.uniprot.org/citations/17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17452518 | http://www.w3.org/2000/01/rdf-schema#comment | "As the rates of most cancers are proportional to the fourth to fifth power of age ("log-log" behavior), it is widely believed that 5 to 6 independent mutations are necessary for malignant transformation. Conversely, the peak incidences of most cancers are similar to stem-cell mutation rates at single loci, implying only one rate-limiting mutation. Here, flow cytometrically measured red blood cells mutated at a selectively neutral locus, glycophorin A, allow observation of individual stem-cell differentiation events in a log-log malignancy, polycythemia rubra vera. Contrary to predictions from multistep models, the clone is driven by infrequent (< annual) and rare ( approximately 18 per year) differentiation events. These parameters imply that malignant stem cells have a modest selective advantage. Correspondingly minor, typically less than 20%, increases in stochastic self-renewal ratios are modeled to show that single mutations can result in the observed fourth power relationship with age. The conundrum between log-log behavior and mutation rate is thereby reconcilable, with the age of onset arising not from the requirement for multiple, independent mutations but from infrequent, stochastic stem-cell division rates and single mutations causing initially minor effects, but initiating a clone whose expected number increases successively with age--an "exponential phenotype.""xsd:string |
| http://purl.uniprot.org/citations/17452518 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2006-12-061911"xsd:string |
| http://purl.uniprot.org/citations/17452518 | http://purl.uniprot.org/core/author | "Vickers M.A."xsd:string |
| http://purl.uniprot.org/citations/17452518 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17452518 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/17452518 | http://purl.uniprot.org/core/pages | "1675-1680"xsd:string |
| http://purl.uniprot.org/citations/17452518 | http://purl.uniprot.org/core/title | "JAK2 617V>F positive polycythemia rubra vera maintained by approximately 18 stochastic stem-cell divisions per year, explaining age of onset by a single rate-limiting mutation."xsd:string |
| http://purl.uniprot.org/citations/17452518 | http://purl.uniprot.org/core/volume | "110"xsd:string |
| http://purl.uniprot.org/citations/17452518 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17452518 |
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| http://purl.uniprot.org/uniprot/#_A0A2R8Y7F9-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
| http://purl.uniprot.org/uniprot/#_A0A2S1CSI3-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
| http://purl.uniprot.org/uniprot/#_E9PD10-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
| http://purl.uniprot.org/uniprot/#_A0A0C4DFT7-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
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| http://purl.uniprot.org/uniprot/#_A9QVL8-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
| http://purl.uniprot.org/uniprot/#_A0A7G1PFV2-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
| http://purl.uniprot.org/uniprot/#_A0A8E8D7U9-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
| http://purl.uniprot.org/uniprot/#_A0A8E8D9B7-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
| http://purl.uniprot.org/uniprot/#_A8K910-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |
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| http://purl.uniprot.org/uniprot/#_B8Q183-mappedCitation-17452518 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17452518 |