Network-based analysis of heterogeneous patient-matched brain and extracranial melanoma metastasis pairs reveals three homogeneous subgroups

Research output: Contribution to journalResearch articleContributedpeer-review


Melanoma, the deadliest form of skin cancer, can metastasize to different organs. Molecular differences between brain and extracranial melanoma metastases are poorly understood. Here, promoter methylation and gene expression of 11 heterogeneous patient-matched pairs of brain and extracranial metastases were analyzed using melanoma-specific gene regulatory networks learned from public transcriptome and methylome data followed by network-based impact propagation of patient-specific alterations. This innovative data analysis strategy allowed to predict potential impacts of patient-specific driver candidate genes on other genes and pathways. The patient-matched metastasis pairs clustered into three robust subgroups with specific downstream targets with known roles in cancer, including melanoma (SG1: RBM38, BCL11B, SG2: GATA3, FES, SG3: SLAMF6, PYCARD). Patient subgroups and ranking of target gene candidates were confirmed in a validation cohort. Summarizing, computational network-based impact analyses of heterogeneous metastasis pairs predicted individual regulatory differences in melanoma brain metastases, cumulating into three consistent subgroups with specific downstream target genes.


Original languageEnglish
Pages (from-to)1036-1050
Number of pages15
JournalComputational and Structural Biotechnology Journal
Publication statusPublished - Dec 2024

External IDs

PubMedCentral PMC10920107
Scopus 85186495835
ORCID /0000-0003-4340-0402/work/155291650
ORCID /0000-0003-4340-9706/work/155292321
ORCID /0000-0002-2844-053X/work/155292471