Jens Luebeck

Nov 6, 2024 | nature.com | Oriol Pich |Kerstin Thol |Jens Luebeck |Natasha E. Weiser |Wei-Ting Lu |Brooke E. Howitt | +11 more

AbstractExtrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer1,2. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.1% of tumour samples contain ecDNA.

Nov 6, 2024 | nature.com | L. T. Hung |Britney Jiayu He |Jens Luebeck |Lotte Brückner |Xiaowei Yan |Rocio Gonzalez | +8 more

AbstractThe chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently1. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division2,3. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells4.

Oct 25, 2024 | biorxiv.org | Imran Noorani |Magnus J. Haughey |Jens Luebeck |Andrew Rowan

AbstractOncogene amplification on extrachromosomal DNA (ecDNA) is strongly associated with treatment resistance and shorter survival for patients with cancer, including patients with glioblastoma. The non-chromosomal inheritance of ecDNA during cell division is a major contributor to intratumoral genetic heterogeneity. At present, the spatial dynamics of ecDNA, and the impact on tumor evolutionary trajectories, are not well understood.

Jun 19, 2024 | elifesciences.org | Miin S. Lin |Se-Young Jo |Jens Luebeck |Howard Chang

eLife assessment This study of extrachromosomal DNA (ecDNA) identifies genes that distinguish ecDNA+ and ecDNA- tumors. The findings in the manuscript are important and the genomic analyses convincing. However, some of the data remain observational and the inferences would therefore be more robust with experimental validation. This manuscript could well be of relevance to biologists interested in cancer biology and gene regulation.

Jun 7, 2023 | nature.com | Albert S Agustinus |Stephanie Stransky |Lorenzo Scipioni |Jens Luebeck |Robert Myers |Britta Weigelt | +13 more

AbstractChromosomal instability (CIN) and epigenetic alterations are characteristics of advanced and metastatic cancers1,2,3,4, but whether they are mechanistically linked is unknown. Here we show that missegregation of mitotic chromosomes, their sequestration in micronuclei5,6 and subsequent rupture of the micronuclear envelope7 profoundly disrupt normal histone post-translational modifications (PTMs), a phenomenon conserved across humans and mice, as well as in cancer and non-transformed cells.