Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/33241418http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33241418http://www.w3.org/2000/01/rdf-schema#comment"

Aims

Somatic mutations of the epigenetic regulators DNMT3A and TET2 causing clonal expansion of haematopoietic cells (clonal haematopoiesis; CH) were shown to be associated with poor prognosis in chronic ischaemic heart failure (CHF). The aim of our analysis was to define a threshold of variant allele frequency (VAF) for the prognostic significance of CH in CHF.

Methods and results

We analysed bone marrow and peripheral blood-derived cells from 419 patients with CHF by error-corrected amplicon sequencing. Cut-off VAFs were optimized by maximizing sensitivity plus specificity from a time-dependent receiver operating characteristic (ROC) curve analysis from censored data. 56.2% of patients were carriers of a DNMT3A- (N = 173) or a TET2-(N = 113) mutation with a VAF >0.5%, with 59 patients harbouring mutations in both genes. Survival ROC analyses revealed an optimized cut-off value of 0.73% for TET2- and 1.15% for DNMT3A-CH-driver mutations. Five-year-mortality was 18% in patients without any detected DNMT3A- or TET2 mutation (VAF < 0.5%), 29% with only one DNMT3A- or TET2-CH-driver mutations above the respective cut-off level and 42% in patients harbouring both DNMT3A- and TET2-CH-driver mutations above the respective cut-off levels. In carriers of a DNMT3A mutation with VAF ≥ 1.15%, 5-year mortality was 31%, compared with 18% mortality in those with VAF < 1.15% (P = 0.048). Likewise, in patients with TET2 mutations, 5-year mortality was 32% with VAF ≥ 0.73%, compared with 19% mortality with VAF < 0.73% (P = 0.029).

Conclusion

The present study defines novel threshold levels for clone size caused by acquired somatic mutations in the CH-driver genes DNMT3A and TET2 that are associated with worse outcome in patients with CHF."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.org/dc/terms/identifier"doi:10.1093/eurheartj/ehaa845"xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Hoffmann J."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Rieger M.A."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Herrmann E."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Cremer S."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Dimmeler S."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Zeiher A.M."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Seeger F."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Kiefer K."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Assmus B."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Abou-El-Ardat K."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Kirschbaum K."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Berkowitsch A."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Dorsheimer L."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Rasper T."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Culmann D."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/author"Mas-Peiro S."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/name"Eur Heart J"xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/pages"257-265"xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/title"Clonal haematopoiesis in chronic ischaemic heart failure: prognostic role of clone size for DNMT3A- and TET2-driver gene mutations."xsd:string
http://purl.uniprot.org/citations/33241418http://purl.uniprot.org/core/volume"42"xsd:string
http://purl.uniprot.org/citations/33241418http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33241418
▶