Center for Application of Advanced Clinical Proteomic Technologies for Cancer (NCI U24; 59963)
EMSL Project ID
46206
Abstract
The overall objective of the PNNL Clinical Proteome Characterization Center (PCPCC) is to facilitate cancer biomarker development by linking the cancer genotype to the cancer phenotype using detailed comprehensive and quantitative characterization of cancer proteomes to complement the extensive genome-level characterization provided by The Cancer Genome Atlas (TCGA). The PCPCC will contribute to the success of the planned network of Protein Characterization Centers (PPCs) by utilizing robust and quantitative proteomics technologies and workflows, including simultaneous application of state-of-the-art validated platforms and advanced developmental platforms, for systematic discovery and verification of protein biomarkers that can be qualified in clinical studies, using the cancer specimens and associated data provided by the CPTC. The Discovery Unit will make measurements providing a comprehensive and quantitative characterization of the cancer proteomes that provides information including protein abundances, splicing variants, mutations, and posttranslational modifications to complement the genomic characterization for CPTC-supplied biospecimens. The extensive database of genomic information on these samples will be integrated with the quantitative proteomic measurements made by the PCPCC, other available proteomics information (e.g., from other PCC's), and a systems-level analysis of tumor-specific pathways to produce a prioritized list of highly credentialed candidates based on a weighted integration of multiple sources of information, including clinical oncology and cancer biology. The Verification Unit will systemically develop and apply multiplexed verification assays directed at specific protein targets as identified and selected by the Biomarker Candidate Selection Subcommittee. The PCPCC will develop sensitive, selective, quantitative assays for a minimum of 100 protein targets per year and apply ultra-sensitive assays to biomarker verification with a throughput of at least 200 plasma (or serum) samples per year, for a total of at least 1000 samples. Additionally, as in the Discovery efforts, measurements with the best available validated platform will be augmented by measurements with a developmental high performance platform for the same samples to provide quantitative measurements for low-abundance otherwise undetectable candidates. As part of a consortium of PCC's, the PCPCC will also work to advance the efforts of others based upon e.g. the cancer tumor proteomics data generated, as well as subsequent biomarker clinical qualification and validation efforts.
Project Details
Start Date
2012-01-16
End Date
2014-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Mass spectrometry for translational proteomics: progress and clinical implications
Baker ES, T Liu, VA Petyuk, KE Burnum-Johnson, YM Ibrahim, GA Anderson, and RD Smith. 2012. "Mass Spectrometry for Translational Proteomics: Progress and Clinical Implications." Genome Medicine 4:Article No. 63. doi:10.1186/gm364
Mass spectrometry-based proteomics: existing capabilities and future directions
Angel TE, UK Aryal, SM Hengel, ES Baker, RT Kelly, EW Robinson, and RD Smith. 2012. "Mass spectrometry-based proteomics: existing capabilities and future directions." Chemical Society Reviews 41(10):3912-3928. doi:10.1039/C2CS15331A