Integrative Genomic Analyses of Patient-Matched Intracranial and Extracranial Metastases Reveal a Novel Brain-Specific Landscape of Genetic Variants in Driver Genes of Malignant Melanoma.
Renata VaraljaiSusanne HornAntje SuckerDaniela PiercianekVerena SchmittAlexander CarpinteiroKatrin Anne BeckerJulia ReifenbergerAlexander RoeschJoerg FelsbergGuido ReifenbergerUlrich SureDirk SchadendorfIris HelfrichPublished in: Cancers (2021)
In our study, 54 intracranial and 18 corresponding extracranial melanoma metastases were analyzed for mutations using targeted next generation sequencing of 29 recurrently mutated driver genes in melanoma. In 11 of 16 paired samples, we detected nucleotide modifications in brain metastases that were absent in matched metastases at extracranial sites. Moreover, we identified novel genetic variants in ARID1A, ARID2, SMARCA4 and BAP1, genes that have not been linked to brain metastases before; albeit most frequent mutations were found in ARID1A, ARID2 and BRAF. Conclusion: Our data provide new insights into the genetic landscape of intracranial melanoma metastases supporting a branched evolution model of metastasis formation.
Keyphrases
- brain metastases
- genome wide
- small cell lung cancer
- internal carotid artery
- copy number
- dna methylation
- genome wide identification
- single cell
- optic nerve
- bioinformatics analysis
- skin cancer
- white matter
- machine learning
- genome wide analysis
- case report
- electronic health record
- gene expression
- drug delivery
- big data
- transcription factor
- optical coherence tomography