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Massively Parallel Molecular Profiling of Breast Cancer


EMSL Project ID
48668

Abstract

Molecular profiling of breast cancer into subcategories based on functional ER expression and amplification of HER2 has significantly enhanced our understanding of the disease, and has pointed the way to broad categories of therapeutic intervention. However, even within the currently recognized subtypes significant levels of heterogeneity are observed in outcomes and response to therapy, particularly in those subtypes resistant to hormonal therapy; e.g. the ‘triple negative’ (ER negative PR negative HER2 negative, or ER-PR-HER2- ) subtype, the ER negative HER2 positive (ER- HER2+) subtype, and the Luminal B subtype. We hypothesize that the clinical heterogeneity of functionally ER- breast cancers is a manifestation of not only differences in gene expression, but also in the functional status and post-translational modifications of the associated proteins that are reflective of the combined effects of population and disease heterogeneity. Thus, robust integration of genomic and broad proteomic data (including global proteomics, phosphoproteomics, O-GlcNAc proteomics, peptidomics and glycomics) from the same patient samples, procured and analyzed under defined protocols, has the potential to provide more effective stratification of patients for prognosis and therapy.

Project Details

Start Date
2014-11-03
End Date
2017-09-30
Status
Closed

Team

Principal Investigator

Richard Smith
Institution
Pacific Northwest National Laboratory

Team Members

Jason McDermott
Institution
Pacific Northwest National Laboratory

Bobbie-Jo Webb-Robertson
Institution
Pacific Northwest National Laboratory

Marina Gritsenko
Institution
Pacific Northwest National Laboratory

Tao Liu
Institution
Pacific Northwest National Laboratory

David Camp
Institution
Pacific Northwest National Laboratory

Karin Rodland
Institution
Pacific Northwest National Laboratory

Related Publications

Wu C, ME Monroe, Z Xu, GW Slysz, SH Payne, KD Rodland, T Liu, and RD Smith. 2015. "An Optimized Informatics Pipeline for Mass Spectrometry-Based Peptidomics." Journal of the American Society for Mass Spectrometry . doi:10.1007/s13361-015-1169-z [In Press]