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@ARTICLE{Ng:295835,
author = {A. W. T. Ng and D. P. McClurg and B. Wesley and S. A.
Zamani and E. Black and A. Miremadi and O. Giger and R. T.
Hoopen and G. Devonshire and A. M. Redmond and N. Grehan and
S. Jammula and A. Blasko and X. Li and S. Aparicio and S.
Tavaré and O. C. Clinical and K. Nowicki-Osuch and R. C.
Fitzgerald},
collaboration = {M. Stratification},
othercontributors = {P. A. W. Edwards and N. Grehan and B. Nutzinger and C.
Loreno and S. Abbas and A. Freeman and E. C. Smyth and M.
O'Donovan and A. Miremadi and S. Malhotra and M. Tripathi
and C. Cheah and H. Coles and C. Millington and M. Eldridge
and M. Secrier and S. Jammula and J. Davies and C. Crichton
and N. Carroll and R. H. Hardwick and P. Safranek and A.
Hindmarsh and V. Sujendran and S. J. Hayes and Y. Ang and A.
Sharrocks and S. R. Preston and I. Bagwan and V. Save and R.
J. E. Skipworth and T. R. Hupp and J. R. O'Neill and O.
Tucker and A. Beggs and P. Taniere and S. Puig and G.
Contino and T. J. Underwood and R. C. Walker and B. L. Grace
and J. Lagergren and J. Gossage and A. Davies and F. Chang
and U. Mahadeva and V. Goh and F. D. Ciccarelli and G.
Sanders and R. Berrisford and D. Chan and E. Cheong and B.
Kumar and L. Sreedharan and S. L. Parsons and I. Soomro and
P. Kaye and J. Saunders and L. Lovat and R. Haidry and M.
Scott and S. Sothi and S. Lishman and G. B. Hanna and C. J.
Peters and K. Moorthy and A. Grabowska and R. Turkington and
D. McManus and H. Coleman and R. D. Petty and F. Bartlet},
title = {{D}isentangling oncogenic amplicons in esophageal
adenocarcinoma.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-02655},
pages = {4074},
year = {2024},
abstract = {Esophageal 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.},
keywords = {Humans / Esophageal Neoplasms: genetics / Esophageal
Neoplasms: pathology / Adenocarcinoma: genetics /
Adenocarcinoma: pathology / Organoids: pathology / Gene
Amplification / DNA Methylation / Oncogenes: genetics / Male
/ Sequence Analysis, DNA: methods / Clonal Evolution:
genetics / Female},
cin = {C150},
ddc = {500},
cid = {I:(DE-He78)C150-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38744814},
pmc = {pmc:PMC11094127},
doi = {10.1038/s41467-024-47619-4},
url = {https://inrepo02.dkfz.de/record/295835},
}