L. T. Hung

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Articles

Origins and impact of extrachromosomal DNA - Nature

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.
Coordinated inheritance of extrachromosomal DNAs in cancer cells - Nature

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.
Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma - Nature Genetics

Nov 9, 2023 | nature.com | Meghana S. Pagadala |Jon Larson |L. T. Hung |Nicole G. Coufal |Howard Chang |Jesse R. Dixon | +8 more

AbstractCircular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%).
The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner - Nature Communications

Apr 28, 2023 | nature.com | Katja Pekrun |Shinnosuke Tsuji |L. T. Hung |Howard Chang

AbstractRecombinant adeno-associated viral vectors (rAAVs) are among the most commonly used vehicles for in vivo based gene therapies. However, it is hard to predict which AAV capsid will provide the most robust expression in human subjects due to the observed discordance in vector-mediated transduction between species.