Method development
ecDNA is small and heavily rearranged, and existing methods are not sufficient to characterize it. We have therefore developed our own: scEC&T-seq, an experimental and computational technique that profiles the transcriptome and ecDNA sequence of single cells (Chamorro González et al., Nat. Genetics, 2023), and Decoil, a purely computational technique that reconstructs ecDNA structure from […]
Understanding ecDNA maintenance and transcription
It is remarkable that cancer cells can maintain and transcribe ecDNA, which is non-chromosomal, circular and does not have centromeres. We hypothesize that specific processes are necessary for ecDNA maintenance and transcription, and that disrupting them can cause loss of ecDNA-based transcripts and lead to cell death of ecDNA-positive tumor cells specifically. Together with the […]
Mechanisms and consequences of ecDNA evolution
ecDNA functions as an evolutionary hotspot, allowing cancers to escape therapy after an initially promising response. We have shown that ecDNA in neuroblastoma is a major source of somatic rearrangements, leading to further circularization or to the reintegration of circular DNA into the linear genome (Koche et al., Nat. Genetics, 2020). In collaboration with the […]
Emergence of ecDNA as an oncogenic driver
In recent years, it has become apparent that extrachromosomal DNA (ecDNA) is a vehicle for oncogene amplification in most cancers and is associated with worse disease prognosis. What is necessary for ecDNA-positive tumors to develop is not yet fully clear. DNA breakage is a prerequisite for circularization, and we are currently mapping where the genome […]