- Titel
- Patient-specific identification of genome-wide DNA-methylation differences between intracranial and extracranial melanoma metastases
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-961390
- Quellenangabe
- Scientific reports
Erscheinungsjahr: 2023
Jahrgang: 13
E-ISSN: 2045-2322
Artikelnummer: 444 - Erstveröffentlichung
- 2023
- Abstract (EN)
- Melanomas frequently metastasize to distant organs and especially intracranial metastases still represent a major clinical challenge. Epigenetic reprogramming of intracranial metastases is thought to be involved in therapy failure, but so far only little is known about patient-specific DNA-methylation differences between intra- and extracranial melanoma metastases. Hierarchical clustering of the methylomes of 24 patient-matched intra- and extracranial melanoma metastases pairs revealed that intra- and extracranial metastases of individual patients were more similar to each other than to metastases in the same tissue from other patients. Therefore, a personalized analysis of each metastases pair was done by a Hidden Markov Model to classify methylation levels of individual CpGs as decreased, unchanged or increased in the intra- compared to the extracranial metastasis. The predicted DNA-methylation alterations were highly patient-specific differing in the number and methylation states of altered CpGs. Nevertheless, four important general observations were made: (i) intracranial metastases of most patients mainly showed a reduction of DNA-methylation, (ii) cytokine signaling was most frequently affected by differential methylation in individual metastases pairs, but also MAPK, PI3K/Akt and ECM signaling were often altered, (iii) frequently affected genes were mainly involved in signaling, growth, adhesion or apoptosis, and (iv) an enrichment of functional terms related to channel and transporter activities supports previous findings for a brain-like phenotype. In addition, the derived set of 17 signaling pathway genes that distinguished intra- from extracranial metastases in more than 50% of patients included well-known oncogenes (e.g. PRKCA, DUSP6, BMP4) and several other genes known from neuronal disorders (e.g. EIF4B, SGK1, CACNG8). Moreover, associations of gene body methylation alterations with corresponding gene expression changes revealed that especially the three signaling pathway genes JAK3, MECOM, and TNXB differ strongly in their expression between patient-matched intra- and extracranial metastases. Our analysis contributes to an in-depth characterization of DNA-methylation differences between patient-matched intra- and extracranial melanoma metastases and may provide a basis for future experimental studies to identify targets for new therapeutic approaches.
- Andere Ausgabe
- Link zum Artikel, der zuerst in der Zeitschrift „Scientific reports” im Verlag Springer Nature erschienen ist.
DOI: 10.1038/s41598-022-24940-w - Verweis
- Ergänzendes Material ist unter folgendem Link zu finden.
Link: https://www.nature.com/articles/s41598-022-24940-w#additional-information - Freie Schlagwörter (EN)
- Cancer, Cancer genomics, Computational biology and bioinformatics, Data mining, Metastasis, Microarrays, Skin cancer
- Klassifikation (DDC)
- 500
- 600
- Verlag
- Springer Nature, London
- Förder- / Projektangaben
- Bundesministerium für Bildung und Forschung (BMBF)
In vitro-Validierung essentieller Kandidaten und übergeordneter Signalwege verantwortlich für die Entstehung und Resistenzentwicklung von Melanom-Hirnmetastasen
ID: 01ZX1913A - Bundesministerium für Bildung und Forschung (BMBF)
e:Med Junior Research Alliance Grant
Integrative Multi-Omics-Daten-Analysen und modellbasierte Therapieprädiktion für Melanom-Hirnmetastasen
ID: 01ZX1913B - Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:14-qucosa2-961390
- Veröffentlichungsdatum Qucosa
- 06.11.2025
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY 4.0