PXD012845-1

PXD012845 is an original dataset announced via ProteomeXchange.

Title	APOBEC mutagenesis and copy number alterations are drivers of proteogenomic tumor evolution and heterogeneity in metastatic thoracic tumors
Description	Intratumor mutational heterogeneity has been documented in primary non-small cell lung cancer. Here, we elucidate mechanisms of tumor evolution and heterogeneity in metastatic thoracic tumors (lung adenocarcinoma and thymic carcinoma) using whole-exome and transcriptome sequencing, SNP array for copy number alterations (CNA) and mass spectrometry-based quantitative proteomics of metastases obtained by rapid autopsy. APOBEC-mutagenesis, promoted by increased expression of APOBEC3 region transcripts and associated with a high-risk germline APOBEC3 variant, strongly correlated with mutational tumor heterogeneity. TP53 mutation status was associated with APOBEC hypermutator status. Interferon pathways were enriched in tumors with high APOBEC mutagenesis and IFN- induced expression of APOBEC3B in lung adenocarcinoma cells in culture suggesting a role for the immune microenvironment in the generation of mutational heterogeneity. CNA occurring late in tumor evolution correlated with downstream transcriptomic and proteomic heterogeneity, although global proteomic heterogeneity was significantly greater than transcriptomic and CNA heterogeneity. These results illustrate key mechanisms underlying multi-dimensional heterogeneity in metastatic thoracic tumors.
HostingRepository	PRIDE
AnnounceDate	2019-05-07
AnnouncementXML	Submission_2019-05-07_09:21:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Udayan Guha
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-22 08:20:28	ID requested
⏵ 1	2019-05-07 09:21:55	announced
2	2024-10-22 04:53:40	announced	2024-10-22: Updated project metadata.

Roper N, Gao S, Maity TK, Banday AR, Zhang X, Venugopalan A, Cultraro CM, Patidar R, Sindiri S, Brown AL, Goncearenco A, Panchenko AR, Biswas R, Thomas A, Rajan A, Carter CA, Kleiner DE, Hewitt SM, Khan J, Prokunina-Olsson L, Guha U, APOBEC Mutagenesis and Copy-Number Alterations Are Drivers of Proteogenomic Tumor Evolution and Heterogeneity in Metastatic Thoracic Tumors. Cell Rep, 26(10):2651-2666.e6(2019) [pubmed]

submitter keyword: tumor heterogeneity rapid autopsy, proteomics

Udayan Guha
contact affiliation	1Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
contact email	udayan.guha@nih.gov
lab head
Udayan Guha
contact affiliation	NCI/NIH
contact email	udayan.guha@nih.gov
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/2019/05/PXD012845

PRIDE project URI

• PRIDE
  1. PXD012845
     1. Label: PRIDE project
     2. Name: APOBEC mutagenesis and copy number alterations are drivers of proteogenomic tumor evolution and heterogeneity in metastatic thoracic tumors