PXD045526

PXD045526 is an original dataset announced via ProteomeXchange.

Title	Breast cancer risk SNPs converge on estrogen receptor binding sites commonly shared between breast tumors to locally alter estrogen signalling output
Description	Estrogen Receptor alpha (ERa) is the main driver of luminal breast cancer development and progression, and represents the main drug target in patient care. ERa chromatin binding has been extensively studied in breast cancer cell lines and a number of human tumors, often focused on differential binding patterns between groups or conditions. However, little is known about the inter-tumor heterogeneity of ERa chromatin action. Here, we use a large set of ERa ChIP-seq data from 70 ERa+ breast cancers (40 women & 30 men) to explore general inter-patient heterogeneity in ERa DNA binding in breast cancers. We found a total universe of 84,565 and 101,653 ERa sites in females and males respectively, with merely 1.2% and 5% of sites shared in at least half of the tumors analyzed, reflecting a high level of inter-patient heterogeneity. This heterogeneity was found to be most variable at putative enhancers as opposed to promoter regions, potentially reflecting a level of functional redundancy in enhancer action. Interestingly, commonly shared ERa sites showed the highest estrogen-driven enhancer activity, as determined using a massive parallel reporter assay, and were most-engaged in long-range chromatin interactions. In addition, the most-commonly shared ERa-occupied enhancers were found enriched for breast cancer risk SNP loci. We experimentally illustrate such SNVs can impact chromatin binding potential for ERa and its pioneer factor FOXA1. Finally, in the TCGA breast cancer cohort, we could confirm these variations to associate with differences in expression for the target gene. Cumulatively, our data reveal a natural hierarchy of ERa-chromatin interactions in breast cancers within a highly heterogeneous inter-tumor ERa landscape, with the most-common shared regions being most active and affected by germline functional risk SNPs for breast cancer development.
HostingRepository	PRIDE
AnnounceDate	2024-05-22
AnnouncementXML	Submission_2024-05-22_11:34:25.149.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	S Stelloo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-20 08:39:09	ID requested
⏵ 1	2024-05-22 11:34:26	announced

10.1101/gr.278680.123;

Joosten SEP, Gregoricchio S, Stelloo S, Yap, ı, c, ı E, Huang CF, Yavuz K, Donaldson Collier M, Morova T, Altinta, ş UB, Kim Y, Canisius S, Moelans CB, van Diest PJ, Korkmaz G, Lack NA, Vermeulen M, Linn SC, Zwart W, Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions. Genome Res, 34(4):539-555(2024) [pubmed]

submitter keyword: Breast Cancer, Estrogen receptor, enhancers,SNPs, rs9952980

Prof. Michiel Vermeulen
contact affiliation	Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen,6525 GA, The Netherlands (lab head)
contact email	m.vermeulen@science.ru.nl
lab head
S Stelloo
contact affiliation	Department of Molecular Biology, Faculty of Science Radboud Institute for Molecular Like Sciences, Radboud University Nijmegen, Nijmegen, 6525 GA, The Netherlands
contact email	Stelloo@science.ru.nl
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/2024/05/PXD045526

PRIDE project URI

• PRIDE
  1. PXD045526
     1. Label: PRIDE project
     2. Name: Breast cancer risk SNPs converge on estrogen receptor binding sites commonly shared between breast tumors to locally alter estrogen signalling output