PXD010779 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Quantitative mass spectrometry to interrogate proteomic heterogeneity in metastatic lung adenocarcinoma and validate a novel somatic mutation CDK12-G879V |
Description | Lung cancer is the leading cause of cancer death both in men and women. Tumor heterogeneity is an impediment to targeted treatment of all cancers, including lung cancer. Here, we sought to characterize changes in tumor proteome and phosphoproteome by longitudinal, prospective collection of tumor tissue of an exceptional responder lung adenocarcinoma patient who survived with metastatic lung adenocarcinoma for more than seven years with HER2-directed therapy in combination with chemotherapy. We employed “Super-SILAC” and TMT labeling strategies to quantify the proteome and phosphoproteome of a lung metastatic site and ten different metastatic progressive lymph nodes collected across a span of seven years, including five lymph nodes procured at autopsy. We identified specific signaling networks enriched in lung compared to the lymph node metastatic sites. We correlated the changes in protein abundance with changes in copy number alteration (CNA) and transcript expression. To further interrogate the mass spectrometry data, patient-specific database was built incorporating all the somatic variants identified by whole genome sequencing (WGS) of genomic DNA from the lung, one lymph node metastatic site and blood. An extensive validation pipeline was built for confirmation of variant peptides. We validated 360 spectra corresponding to 55 germline and 6 somatic variant peptides. Targeted MRM assays demonstrated expression of two novel variant somatic peptides, CDK12 G879V and FASN-R1439Q, with expression in lung and lymph node metastatic sites, respectively. CDK12 G879V mutation likely results in a nonfunctional kinase and knockdown of CDK12 in lung adenocarcinoma cells increased chemotherapy sensitivity, explaining the complete resolution of the lung metastatic sites in this patient. |
HostingRepository | PRIDE |
AnnounceDate | 2019-01-07 |
AnnouncementXML | Submission_2019-01-07_09:48:18.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 | phosphorylated residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-08-15 02:48:52 | ID requested | |
⏵ 1 | 2019-01-07 09:48:19 | announced | |
2 | 2019-01-11 01:20:46 | announced | Updated publication reference for PubMed record(s): 30617155. |
Publication List
Dataset with its publication pending |
Keyword List
curator keyword: Biomedical |
submitter keyword: proteomic heterogeneity, lung adenocarcinoma, quantitative mass spectrometry |
Contact List
Udayan Guha |
contact affiliation | Thoracic and Gastrointestinal Oncology Branch, CCR , NCI, NIH |
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
- PXD010779
- Label: PRIDE project
- Name: Quantitative mass spectrometry to interrogate proteomic heterogeneity in metastatic lung adenocarcinoma and validate a novel somatic mutation CDK12-G879V