Preservation and Clonal Behavior of Extrachromosomal DNA in Patient-Derived Xenograft Models of Childhood Cancers
Kenkre, R.; Larson, J. D.; Chapman, O. S.; Luebeck, J.; Lo, Y. Y.; Paul, M.; Zhang, W.; Bafna, V.; Wechsler-Reya, R.; Chavez, L.
Show abstract
Extrachromosomal DNA (ecDNA) is a powerful oncogenic driver linked to poor prognosis in pediatric cancers. Whole-genome sequencing of 338 patient-derived xenograft (PDX) samples and 127 matched primary tumors across multiple childhood cancer types was used to compare ecDNA prevalence, sequence conservation, and clonal dynamics. ecDNA in PDX models frequently mirrored oncogene amplifications observed in patient tumors (e.g., MYCN, MYC, MDM2) and showed high sequence conservation. Medulloblastoma and neuroblastoma PDXs exhibited significantly higher ecDNA prevalence, consistent with strong selection or de novo formation during tumor propagation. Although ecDNA copy numbers were generally preserved, some neuroblastoma PDXs displayed marked MYCN copy gains. Single-cell multiome profiling revealed that ecDNA-positive clones either persisted or expanded dramatically in PDXs, in one case growing from a minor subpopulation to nearly all tumor cells. These findings establish PDX models as valuable systems for ecDNA research and underscore the selective growth advantage conferred by ecDNA during tumor evolution.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features 95%
- Single cell transcriptomic profiling identifies tumor-acquired and therapy-resistant cell states in pediatric rhabdomyosarcoma 95%
- Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution. 94%
Similar papers in this journal
- Single cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers 94%
- An integrated single-cell RNA-seq map of human neuroblastoma tumors and preclinical models uncovers divergent mesenchymal-like gene expression programs. 92%
- RNA allelic frequencies of somatic mutations encode substantial functional information in cancers 92%
Similar papers in this journal
- Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma 93%
- Pan-cancer association of DNA repair deficiencies with whole-genome mutational patterns 92%
- Increased Burden of Familial-associated Early-onset Cancer Risk among Latino Americans Compared to non-Latino Whites 92%
Similar papers in this journal
- Long-read RNA sequencing redefines the clear cell renal cell carcinoma transcriptome and reveals novel genes and transcripts associated with disease recurrence and immune evasion 93%
- Somatic structural variation targets neurodevelopmental genes and identifies SHANK2 as a tumor suppressor in neuroblastoma 92%
- Single-cell Rapid Capture Hybridization sequencing (scRaCH-seq) to reliably detect isoform usage and coding mutations in targeted genes at a single-cell level 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.