The Proteomic Landscape of Triple-Negative Breast Cancer

• Published in: Cell reports (Cambridge) Vol. 11; no. 4; pp. 630 - 644
• Main Authors: Lawrence, Robert T., Perez, Elizabeth M., Hernández, Daniel, Miller, Chris P., Haas, Kelsey M., Irie, Hanna Y., Lee, Su-In, Blau, C. Anthony, Villén, Judit
• Format: Journal Article
• Language: English
• Published: United States Elsevier 28.04.2015
• Subjects: Antineoplastic Agents - pharmacology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Drug Resistance, Neoplasm; Female; High-Throughput Screening Assays; Humans; Proteome - drug effects; Proteome - genetics; Proteome - metabolism; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.03.050

Triple-negative breast cancer is a heterogeneous disease characterized by poor clinical outcomes and a shortage of targeted treatment options. To discover molecular features of triple-negative breast cancer, we performed quantitative proteomics analysis of twenty human-derived breast cell lines and four primary breast tumors to a depth of more than 12,000 distinct proteins. We used this data to identify breast cancer subtypes at the protein level and demonstrate the precise quantification of biomarkers, signaling proteins, and biological pathways by mass spectrometry. We integrated proteomics data with exome sequence resources to identify genomic aberrations that affect protein expression. We performed a high-throughput drug screen to identify protein markers of drug sensitivity and understand the mechanisms of drug resistance. The genome and proteome provide complementary information that, when combined, yield a powerful engine for therapeutic discovery. This resource is available to the cancer research community to catalyze further analysis and investigation.