A. Henssen

Quantitative and sensitive neuroblastoma minimal residual disease detection using extrachromosomal DNA (ecDNA) breakpoints

Sensitive detection of minimal residual disease (MRD) remains a major unmet need in high-risk neuroblastoma. MYCN amplification, a hallmark of high-risk disease, typically occurs on extrachromosomal DNA (ecDNA), but the potential of ecDNA-associated genomic rearrangements for individualized MRD monitoring has not been...

The shared evolutionary capacities of plasmids and extrachromosomal DNA.

MMEJ repair of breaks at TA repeats maintains ecDNA and cancer fitness

Extrachromosomal DNA (ecDNA) comprises megabase-sized circular DNA elements that frequently carry oncogene amplifications, driving aggressive tumour phenotypes, therapeutic resistance and poor clinical outcomes across many cancers1, 2, 3–4. Although ecDNA is thought to arise from canonical double-strand break repair, t...

Inverted logic of ecDNA localization converts nuclear periphery into oncogenic transcription hubs in cancer

It is shown that ecDNAs, in contrast to chromosomal DNA, preferentially localize to the nuclear periphery yet resist peripheral gene silencing, and single-molecule multi-omic sequencing and imaging-based CRISPR screening demonstrate enhanced ecDNA hub formation, H3K27ac and H3K9me3 bivalency, late DNA replication, long...