PXD064049-1

PXD064049 is an original dataset announced via ProteomeXchange.

Title	Extrachromosomal DNA-driven oncogene dosage heterogeneity promotes rapid adaptation to therapy in MYCN-amplified cancers
Description	Extrachromosomal DNA (ecDNA) amplification enhances intercellular oncogene dosage variability and accelerates tumor evolution by violating foundational principles of genetic inheritance through its asymmetric mitotic segregation. Spotlighting high-risk neuroblastoma we demonstrate how ecDNA amplification undermines the clinical efficacy of current therapies in cancers with extrachromosomal MYCN amplification. Integrating theoretical models of oncogene copy number-dependent fitness with single-cell ecDNA quantification and phenotype analyses, we reveal that ecDNA copy number heterogeneity drives phenotypic diversity and determines treatment sensitivity through mechanisms unattainable by chromosomal oncogene amplification. We demonstrate that ecDNA copy number directly influences critical cell fate decisions in cancer cell lines, patient-derived xenografts and primary neuroblastomas, illustrating how extrachromosomal oncogene dosage-driven phenotypic diversity offers a strong evolutionary advantage under therapeutic pressure. Furthermore, we identify senescent ecDNA-containing cells with reduced copy numbers in neuroblastomas and other MYC-amplified cancers as a source of treatment resistance and outline a strategy for their targeted elimination to improve the poor outcome of patients with MYCN-amplified cancers.
HostingRepository	PRIDE
AnnounceDate	2025-07-05
AnnouncementXML	Submission_2025-07-05_01:29:31.165.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Coscia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-19 02:27:24	ID requested
⏵ 1	2025-07-05 01:29:31	announced

Dataset with its publication pending

submitter keyword: MYCN,Neuroblastoma, Proteomics

Dr. Fabian Coscia
contact affiliation	Max Delbrück Center Robert-Rössle-Straße 10 13125 Berlin, Germany
contact email	fabian.coscia@mdc-berlin.de
lab head
Fabian Coscia
contact affiliation	Max Delbrück Center
contact email	fabian.coscia@mdc-berlin.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/07/PXD064049

PRIDE project URI

• PRIDE
  1. PXD064049
     1. Label: PRIDE project
     2. Name: Extrachromosomal DNA-driven oncogene dosage heterogeneity promotes rapid adaptation to therapy in MYCN-amplified cancers