PXD012845 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:53:32.706.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 |
Dataset History
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. |
Publication List
10.1016/j.celrep.2019.02.028; |
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] |
Keyword List
submitter keyword: proteomics,tumor heterogeneity rapid autopsy |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD012845
- Label: PRIDE project
- Name: APOBEC mutagenesis and copy number alterations are drivers of proteogenomic tumor evolution and heterogeneity in metastatic thoracic tumors