@article{b7e3518965614a44a0d7774f21e81931,
title = "Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors",
abstract = "Proliferative and invasive breast tumors evolve heterogeneously in individual patients, posing significant challenges in identifying new druggable targets for precision, effective therapy. Here we present a functional multi-omics method, interaction-Correlated Multi-omic Aberration Patterning (iC-MAP), which dissects intra-tumor heterogeneity and identifies in situ the oncogenic consequences of multi-omics aberrations that drive proliferative and invasive tumors. First, we perform chromatin activity-based chemoproteomics (ChaC) experiments on breast cancer (BC) patient tissues to identify genetic/transcriptomic alterations that manifest as oncogenically active proteins. ChaC employs a biotinylated small molecule probe that specifically binds to the oncogenically active histone methyltransferase G9a, enabling sorting/enrichment of a G9a-interacting protein complex that represents the predominant BC subtype in a tissue. Second, using patient transcriptomic/genomic data, we retrospectively identified some G9a interactor-encoding genes that showed individualized iC-MAP. Our iC-MAP findings represent both new diagnostic/prognostic markers to identify patient subsets with incurable metastatic disease and targets to create individualized therapeutic strategies.",
keywords = "Biological Sciences, Cancer, Cancer Systems Biology",
author = "Wrobel, {John A.} and Ling Xie and Li Wang and Cui Liu and Naim Rashid and Gallagher, {Kristalyn K.} and Yan Xiong and Konze, {Kyle D.} and Jian Jin and Gatza, {Michael L.} and Xian Chen",
note = "Funding Information: This work was supported in part by grants NC Tracs TTSA Phase I TTSA021P1 , NIH 1U19AI109965 , 1U24CA160035-01 from the National Cancer Institute Clinical Proteomic Tumor Analysis Consortium (CPTAC) (to X.C.) and R01GM122749 (to J.J.). We thank Dr. Howard Fried for editorial assistance. This invention of iC-MAP is protected by United States Provisional Patent Application Serial No. 62/608,992 that was filed by the University of North Carolina-Chapel Hill. Funding Information: This work was supported in part by grants NC Tracs TTSA Phase I TTSA021P1, NIH 1U19AI109965, 1U24CA160035-01 from the National Cancer Institute Clinical Proteomic Tumor Analysis Consortium (CPTAC) (to X.C.) and R01GM122749 (to J.J.). We thank Dr. Howard Fried for editorial assistance. This invention of iC-MAP is protected by United States Provisional Patent Application Serial No. 62/608,992 that was filed by the University of North Carolina-Chapel Hill. J.A.W. developed the software, performed proteogenomic analysis of clinical data, and wrote the report. L.X. and L.W. performed sample preparation and processing of some cell lines and clinical tissues for MS/MS experimental analysis, analyzed data, and conducted functional characterization. C.L. performed chem-precipitation with UNC0965 for PCR. N.R. M.L.G. and K.K.G. assisted clinicopathological data analysis. Y.X. K.D.K. and J.J. provided UNC0965 and UNC125. X.C. conceived and designed the project and experiments, analyzed and interpreted data, and wrote the manuscript. The invention of ChaC is protected by US Patent Application Serial No. 15/118,061 that was filed by the University of North Carolina-Chapel Hill. Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = jul,
day = "26",
doi = "10.1016/j.isci.2019.07.001",
language = "English",
volume = "17",
pages = "359--378",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
}