Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors
Summary: 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 Patterni...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004219302263 |
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doaj-2190088fe15f4271b01c858f46fc8fc1 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
John A. Wrobel Ling Xie Li Wang Cui Liu Naim Rashid Kristalyn K. Gallagher Yan Xiong Kyle D. Konze Jian Jin Michael L. Gatza Xian Chen |
| spellingShingle |
John A. Wrobel Ling Xie Li Wang Cui Liu Naim Rashid Kristalyn K. Gallagher Yan Xiong Kyle D. Konze Jian Jin Michael L. Gatza Xian Chen Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors iScience |
| author_facet |
John A. Wrobel Ling Xie Li Wang Cui Liu Naim Rashid Kristalyn K. Gallagher Yan Xiong Kyle D. Konze Jian Jin Michael L. Gatza Xian Chen |
| author_sort |
John A. Wrobel |
| title |
Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors |
| title_short |
Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors |
| title_full |
Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors |
| title_fullStr |
Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors |
| title_full_unstemmed |
Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors |
| title_sort |
multi-omic dissection of oncogenically active epiproteomes identifies drivers of proliferative and invasive breast tumors |
| publisher |
Elsevier |
| series |
iScience |
| issn |
2589-0042 |
| publishDate |
2019-07-01 |
| description |
Summary: 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. : Biological Sciences; Cancer Systems Biology; Cancer Subject Areas: Biological Sciences, Cancer Systems Biology, Cancer |
| url |
http://www.sciencedirect.com/science/article/pii/S2589004219302263 |
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doaj-2190088fe15f4271b01c858f46fc8fc12020-11-24T21:54:56ZengElsevieriScience2589-00422019-07-0117359378Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast TumorsJohn A. Wrobel0Ling Xie1Li Wang2Cui Liu3Naim Rashid4Kristalyn K. Gallagher5Yan Xiong6Kyle D. Konze7Jian Jin8Michael L. Gatza9Xian Chen10Department of Biochemistry & Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Biochemistry & Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Biochemistry & Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Biochemistry & Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USALineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biostatistics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USABreast Surgical Oncology and Oncoplastics, UNC Surgical Breast Care Program, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Biochemistry & Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USADepartment of Biochemistry & Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Corresponding authorSummary: 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. : Biological Sciences; Cancer Systems Biology; Cancer Subject Areas: Biological Sciences, Cancer Systems Biology, Cancerhttp://www.sciencedirect.com/science/article/pii/S2589004219302263 |