| 1. |
- Lichti, Cheryl F., et al.
(författare)
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Integrated Chromosome 19 Transcriptomic and Proteomic Data Sets Derived from Glioma Cancer Stem-Cell Lines
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:1, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- One subproject within the global Chromosome 19 Consortium is to define chromosome 19 gene and protein expression in glioma-derived cancer stem cells (GSCs). Chromosome 19 is notoriously linked to glioma by 1p/19q codeletions, and clinical tests are established to detect that specific aberration. GSCs are tumor-initiating cells and are hypothesized to provide a repository of cells in tumors that can self-replicate and be refractory to radiation and chemotherapeutic agents developed for the treatment of tumors. In this pilot study, we performed RNA-Seq, label-free quantitative protein measurements in six GSC lines, and targeted transcriptomic analysis using a chromosome 19-specific microarray in an additional six GSC lines. The data have been deposited to the ProteomeXchange with identifier PXD000563. Here we present insights into differences in GSC gene and protein expression, including the identification of proteins listed as having no or low evidence at the protein level in the Human Protein Atlas, as correlated to chromosome 19 and GSC subtype. Furthermore, the upregulation of proteins downstream of adenovirus-associated integration site 1 (AAVS1) in GSC11 in response to oncolytic adenovirus treatment was demonstrated. Taken together, our results may indicate new roles for chromosome 19, beyond the 1p/19q codeletion, in the future of personalized medicine for glioma patients.
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| 2. |
- Horvatovich, Peter, et al.
(författare)
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Quest for Missing Proteins : Update 2015 on Chromosome-Centric Human Proteome Project
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:9, s. 3415-3431
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wild (http://c-hpp.webhosting.rug.nl/) and in the Supporting Information.
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| 3. |
- Lichti, Cheryl, et al.
(författare)
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Systematic Identification of Single Amino Acid Variants in Glioma Stem-Cell-Derived Chromosome 19 Proteins
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:2, s. 778-786
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Tidskriftsartikel (refereegranskat)abstract
- Novel proteoforms with single amino acid polymorphism represent proteins that often have altered biological functions but are less explored in the human proteome. We have developed an approach, searching high quality shotgun proteomic data against an extended protein database, to identify expressed mutant proteoforms in glioma stem cell (GSC) lines. The systematic search of MS/MS spectra has recognized 13 chromosome 19 proteins in GSCs with altered amino acid sequences using PEAKS 7.0 as the search engine. The results were further verified by manual spectral examination, validating 14 proteoforms. One of the novel findings, a mutant form of branched-chain aminoacyl transferase 2 (T186R), was verified at the transcript level and by SRM in several glioma stem cell lines. The structure of this proteoform examined by molecular modeling to estimate structural changes of mutation that could lead to functional modifications potentially linked to glioma. Based on our initial findings, we believe that our approach presented could contribute to construct a more complete map of the human functional proteome.
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| 4. |
- Mostovenko, Ekaterina, et al.
(författare)
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Combined Proteomic-Molecular Epidemiology Approach to Identify Precision Targets in Brain Cancer
- 2018
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 9:1, s. 80-84
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Tidskriftsartikel (refereegranskat)abstract
- Primary brain tumors are predominantly malignant gliomas. Grade IV astrocytomas (glioblastomas, GBM) are among the most deadly of all tumors; most patients will succumb to their disease within 2 years of diagnosis despite standard of care. The grim outlook for brain tumor patients indicates that novel precision therapeutic targets must be identified. Our hypothesis is that the cancer proteomes of glioma tumors may contain protein variants that are linked to the aggressive pathology of the disease. To this end, we devised a novel workflow that combined variant proteomics with molecular epidemiological mining of public cancer data sets to identify 10 previously unrecognized variants linked to the risk of death in low grade glioma or GBM. We hypothesize that a subset of the protein variants may be successfully developed in the future as novel targets for malignant gliomas.
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| 5. |
- Mostovenko, Ekaterina, et al.
(författare)
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Large Scale Identification of Variant Proteins in Glioma Stem Cells
- 2018
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 9:1, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM), the most malignant of primary brain tumors, is a devastating and deadly disease, with a median survival of 14 months from diagnosis, despite standard regimens of radical brain tumor surgery, maximal safe radiation, and concomitant chemotherapy. GBM tumors nearly always re-emerge after initial treatment and frequently display resistance to current treatments. One theory that may explain GBM re-emergence is the existence of glioma stemlike cells (GSCs). We sought to identify variant protein features expressed in low passage GSCs derived from patient tumors. To this end, we developed a proteomic database that reflected variant and nonvariant sequences in the human proteome, and applied a novel retrograde proteomic workflow, to identify and validate the expression of 126 protein variants in 33 glioma stem cell strains. These newly identified proteins may harbor a subset of novel protein targets for future development of GBM therapy.
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