In: Clinical Sarcoma Research, 7 (2017), Nr. 9. S. 1-11. ISSN 2045-3329
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Abstract
Background: Histone 3.3 (H3.3) hotspot mutations in bone tumors occur in the vast majority of giant cell tumors of bone (GCTBs; 96%), chondroblastomas (95%) and in a few cases of osteosarcomas. However, clinical presentation, histopathological features, and additional molecular characteristics of H3.3 mutant osteosarcomas are largely unknown. Methods: In this multicentre, retrospective study, a total of 106 conventional high-grade osteosarcomas, across all age groups were re-examined for hotspot mutations in the H3.3 coding genes H3F3A and H3F3B. H3.3 mutant osteosarcomas were re-evaluated in a multidisciplinary manner and analyzed for genome-wide DNA-methylation patterns and DNA copy number aberrations alongside H3.3 wild-type osteosarcomas and H3F3A G34W/L mutant GCTBs. Results: Six osteosarcomas (6/106) carried H3F3A hotspot mutations. No mutations were found in H3F3B. All patients with H3F3A mutant osteosarcoma were older than 30 years with a median age of 65 years. Copy number aberrations that are commonly encountered in high-grade osteosarcomas also occurred in H3F3A mutant osteosarcomas. Unlike a single osteosarcoma with a H3F3A K27M mutation, the DNA methylation profiles of H3F3A G34W/R mutant osteosarcomas were clearly different from H3.3 wild-type osteosarcomas, but more closely related to GCTBs. The most differentially methylated promoters between H3F3A G34W/R mutant and H3.3 wild-type osteosarcomas were in KLLN/PTEN (p < 0.00005) and HIST1H2BB (p < 0.0005). Conclusions: H3.3 mutations in osteosarcomas may occur in H3F3A at mutational hotspots. They are overall rare, but become more frequent in osteosarcoma patients older than 30 years. Osteosarcomas carrying H3F3A G34W/R mutations are associated with epigenetic dysregulation of KLLN/PTEN and HIST1H2BB.
Dokumententyp: | Artikel |
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Titel der Zeitschrift: | Clinical Sarcoma Research |
Band: | 7 |
Nummer: | 9 |
Verlag: | BioMed Central |
Ort der Veröffentlichung: | London |
Erstellungsdatum: | 10 Mai 2017 07:31 |
Erscheinungsjahr: | 2017 |
ISSN: | 2045-3329 |
Seitenbereich: | S. 1-11 |
Institute/Einrichtungen: | Zentrale und Sonstige Einrichtungen > Interdisziplinäres Zentrum für Neurowissenschaften
Zentrale und Sonstige Einrichtungen > CellNetworks Core Technology Platform Zentrale und Sonstige Einrichtungen > Deutsches Krebsforschungszentrum Medizinische Fakultät Heidelberg und Uniklinikum > Universitätskinderklinik Medizinische Fakultät Heidelberg und Uniklinikum > Radiologische Universitätsklinik Medizinische Fakultät Heidelberg und Uniklinikum > Pathologisches Institut |
DDC-Sachgruppe: | 610 Medizin |