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000295835 1001_ $$0P:(DE-HGF)0$$aNg, Alvin Wei Tian$$b0
000295835 245__ $$aDisentangling oncogenic amplicons in esophageal adenocarcinoma.
000295835 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000295835 520__ $$aEsophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons' origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma.
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000295835 650_2 $$2MeSH$$aHumans
000295835 650_2 $$2MeSH$$aEsophageal Neoplasms: genetics
000295835 650_2 $$2MeSH$$aEsophageal Neoplasms: pathology
000295835 650_2 $$2MeSH$$aAdenocarcinoma: genetics
000295835 650_2 $$2MeSH$$aAdenocarcinoma: pathology
000295835 650_2 $$2MeSH$$aOrganoids: pathology
000295835 650_2 $$2MeSH$$aGene Amplification
000295835 650_2 $$2MeSH$$aDNA Methylation
000295835 650_2 $$2MeSH$$aOncogenes: genetics
000295835 650_2 $$2MeSH$$aMale
000295835 650_2 $$2MeSH$$aSequence Analysis, DNA: methods
000295835 650_2 $$2MeSH$$aClonal Evolution: genetics
000295835 650_2 $$2MeSH$$aFemale
000295835 7001_ $$0P:(DE-HGF)0$$aMcClurg, Dylan Peter$$b1
000295835 7001_ $$00009-0003-2550-9380$$aWesley, Ben$$b2
000295835 7001_ $$00000-0001-8622-5013$$aZamani, Shahriar A$$b3
000295835 7001_ $$00000-0001-9929-8043$$aBlack, Emily$$b4
000295835 7001_ $$0P:(DE-HGF)0$$aMiremadi, Ahmad$$b5
000295835 7001_ $$0P:(DE-HGF)0$$aGiger, Olivier$$b6
000295835 7001_ $$0P:(DE-HGF)0$$aHoopen, Rogier Ten$$b7
000295835 7001_ $$00000-0002-1408-8176$$aDevonshire, Ginny$$b8
000295835 7001_ $$0P:(DE-HGF)0$$aRedmond, Aisling M$$b9
000295835 7001_ $$0P:(DE-HGF)0$$aGrehan, Nicola$$b10
000295835 7001_ $$0P:(DE-HGF)0$$aJammula, Sriganesh$$b11
000295835 7001_ $$0P:(DE-HGF)0$$aBlasko, Adrienn$$b12
000295835 7001_ $$0P:(DE-HGF)0$$aLi, Xiaodun$$b13
000295835 7001_ $$00000-0002-0487-9599$$aAparicio, Samuel$$b14
000295835 7001_ $$00000-0002-3716-4952$$aTavaré, Simon$$b15
000295835 7001_ $$0P:(DE-HGF)0$$aClinical, Oesophageal Cancer$$b16
000295835 7001_ $$0P:(DE-HGF)0$$aStratification, Molecular$$b17$$eCollaboration Author
000295835 7001_ $$aNowicki-Osuch, Karol$$b18
000295835 7001_ $$00000-0002-3434-3568$$aFitzgerald, Rebecca C$$b19
000295835 7001_ $$0P:(DE-HGF)0$$aEdwards, Paul A W$$b20$$eContributor
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000295835 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-47619-4$$gVol. 15, no. 1, p. 4074$$n1$$p4074$$tNature Communications$$v15$$x2041-1723$$y2024
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