Targeting genome instability in cancer

About Us

We are a group of physicians, experimental and computational biologists at the Experimental and Clinical Research Center (ECRC) of the MDC and Charité Berlin studying extrachromosomal DNA (ecDNA), circular DNA molecules that exist outside the chromosomes and act as vehicles for oncogene amplification. ecDNA amplification occurs frequently across cancer types and is consistently associated with worse prognosis.

 

Our main model is neuroblastoma, a solid tumor of childhood in which a large subgroup of patients carries an amplification of the MYCN oncogene on ecDNA. Such tumors are classified as high-risk, a group with a mortality rate around 50%, making neuroblastoma both a clinically-important problem and a well-defined system in which to study ecDNA biology. The lab studies the emergence, evolution and maintenance of ecDNA in neuroblastoma and other malignancies. Our long-term goal is to determine specific vulnerabilities that can guide clinical trials of personalized treatments for children with ecDNA-positive cancers.

 

We are a highly collaborative lab: approximately half of all projects are co-led by two or more students and combine experimental and computational work. Collaborations, joint lab meetings and workshops with partner labs are a regular part of how we work.

We combine experimental and computational approaches: single-cell and bulk sequencing (scRNA-seq, scG&T-seq, Hi-C, nanopore WGS, among others), microscopy and perturbation techniques, cell and mouse model systems, and computational method development including machine learning.

 

Our PI, Anton Henssen, has received an ERC Starting Grant, an Emmy Noether professorship, and is currently a Mildred Scheel professor. We coordinate a DFG Sonderforschungsbereich on neuroblastoma evolution and a cooperative Jöster Stiftung grant on pediatric tumor evolution and plasticity, and are part of the Cancer Grand Challenges team eDyNAmiC on extrachromosomal DNA.

Key Publications

Extrachromosomal DNA micronucleation constrains tumour fitness and improves patient survival

Brückner L, Xu R, Tang J, Gnanasekar A, Herrmann A, Tsz-Lo Wong I, Zhang S, Tu F, Pilon M, Kukalev A, Pardon K, Sidorova O, Atta J, Yu Q, Montouri G, Pradella D, Ilić M, Suina K, Novais-Cruz M, Kaltenbach S, Treue D, Giurgiu-Kraljič M, Herzog S, Hollinger A, Wittstruck N, Fernandez M, Wolozyn N, Becker F, Louma V, Yan X, Schmargon R, Dörr J, Gamlin D, Lehmann A, Gürgen D, Richter M, Dubois F, Simeoni F, Pennycook BR, Hamilton A, Lindemann RK, Dawes C, Balmus G, Hero B, Fischer M, Bafna V, Verhaak R, Wahl G, Liu Y,  Koche RP, Papathanasiou S, Medema R, Spanjaard B, Ventura A, Pombo A, Huang W, Scheer M, Werner B, Chang HY, Mischel PS, Henssen AG

bioRxiv (2026)

https://www.biorxiv.org/content/10.1101/2025.04.15.648906v2

Extrachromosomal DNA–Driven Oncogene Dosage Heterogeneity Promotes Rapid Adaptation to Therapy in MYCN-Amplified Cancers

Montuori G, Tu F, Qin D, Schmargon R, Rodriguez-Fos E, Helmsauer K, Hui H, Mandal S, Purshouse K, Fankhänel L, Bosco B, Spanjaard B, Seyboldt H, Grunewald L, Schmitt M, Gürgen D, Buck V, Rosenfeldt M, Dubois FPB, Schallenberg S, Lehmann A, Theißen J, Taschner-Mandl S, Koch A, Hundsdoerfer P, Künkele A, Eggert A, Fischer M, Gargiulo G, Krieger TG, Chavez L, Coscia F, Werner B, Huang W, Henssen AG, Dörr J

Cancer Discovery (2025); 15 (10): 2054–2077

https://aacrjournals.org/cancerdiscovery/article/15/10/2054/765955/Extrachromosomal-DNA-Driven-Oncogene-Dosage

Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer

Bei Y, Bramé L, Kirchner M, Fritsche-Guenther R, Kunz S, Bhattacharya A, Rusu M, Gürgen D, Dubios FPB, Köppke JKC, Proba J, Wittstruck N, Sidorova OA, Chamorro González R, Dorado Garcia H, Brückner L, Xu R, Giurgiu M, Rodriguez-Fos E, Yu Q, Spanjaard B, Koche RP, Schmitt CA, Schulte JH, Eggert A, Haase K, Kirwan J, Heeren-Hagemann AI, Mertins P, Dörr JR, Henssen AG

Cancer Discovery (2024) 14 (3): 492–507

https://aacrjournals.org/cancerdiscovery/article/14/3/492/734910/Passenger-Gene-Coamplifications-Create-Collateral

Reconstructing extrachromosomal DNA structural heterogeneity from long-read sequencing data using Decoil

Giurgiu M, Wittstruck N, Rodriguez-Fos E, Chamorro González R, Brückner L, Krienelke-Szymansky A, Helmsauer K, Hartebrodt A, Euskirchen P, Koche RP, Haase K, Reinert K, Henssen AG

Genome Research (2024), Vol. 34 Issue 9, 1355-1364

https://genome.cshlp.org/content/34/9/1355

Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells

Chamorro González R, Conrad T, Stöber MC, Xu R, Giurgiu M, Rodriguez-Fos M, Kasack K, Brückner L, van Leen E, Helmsauer K, Dorado Garcia H, Stefanova ME, Hung KL, Bei Y, Schmelz K, Lodrini M, Mundlos S, Chang HY, Deubzer HE, Sauer S, Eggert A, Schulte JH, Schwarz RF, Haase K, Koche RP, Henssen AG

Nature Genetics (2023) 55, 880–890

https://www.nature.com/articles/s41588-023-01386-y

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