@ARTICLE{Muller2016-mp,
  title    = "Single-cell sequencing maps gene expression to mutational
              phylogenies in {PDGF-} and {EGF-driven} gliomas",
  author   = "M{\"u}ller, S{\"o}ren and Liu, Siyuan John and Di Lullo,
              Elizabeth and Malatesta, Martina and Pollen, Alex A and
              Nowakowski, Tomasz J and Kohanbash, Gary and Aghi, Manish and
              Kriegstein, Arnold R and Lim, Daniel A and Diaz, Aaron",
  abstract = "Glioblastoma multiforme (GBM) is the most common and aggressive
              type of primary brain tumor. Epidermal growth factor (EGF) and
              platelet-derived growth factor (PDGF) receptors are frequently
              amplified and/or possess gain-of-function mutations in GBM
              However, clinical trials of tyrosine-kinase inhibitors have shown
              disappointing efficacy, in part due to intra-tumor heterogeneity.
              To assess the effect of clonal heterogeneity on gene expression,
              we derived an approach to map single-cell expression profiles to
              sequentially acquired mutations identified from exome sequencing.
              Using 288 single cells, we constructed high-resolution
              phylogenies of EGF-driven and PDGF-driven GBMs, modeling
              transcriptional kinetics during tumor evolution. Descending the
              phylogenetic tree of a PDGF-driven tumor corresponded to a
              progressive induction of an oligodendrocyte progenitor-like cell
              type, expressing pro-angiogenic factors. In contrast,
              phylogenetic analysis of an EGFR-amplified tumor showed an
              up-regulation of pro-invasive genes. An in-frame deletion in a
              specific dimerization domain of PDGF receptor correlates with an
              up-regulation of growth pathways in a proneural GBM and enhances
              proliferation when ectopically expressed in glioma cell lines.
              In-frame deletions in this domain are frequent in public GBM
              data.",
  journal  = "Mol Syst Biol",
  volume   =  12,
  number   =  11,
  pages    = "889",
  month    =  nov,
  year     =  2016,
  keywords = "PDGFRA; copy‐number variation; glioblastoma; single‐cell
              RNA‐sequencing; tumor phylogeny",
  language = "en"
}

{"_id":"9ZkoX5JWGTs5tCHqF","bibbaseid":"mller-liu-dilullo-malatesta-pollen-nowakowski-kohanbash-aghi-etal-singlecellsequencingmapsgeneexpressiontomutationalphylogeniesinpdgfandegfdrivengliomas-2016","author_short":["Müller, S.","Liu, S. J.","Di Lullo, E.","Malatesta, M.","Pollen, A. A","Nowakowski, T. J","Kohanbash, G.","Aghi, M.","Kriegstein, A. R","Lim, D. A","Diaz, A."],"bibdata":{"bibtype":"article","type":"article","title":"Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas","author":[{"propositions":[],"lastnames":["Müller"],"firstnames":["Sören"],"suffixes":[]},{"propositions":[],"lastnames":["Liu"],"firstnames":["Siyuan","John"],"suffixes":[]},{"propositions":[],"lastnames":["Di","Lullo"],"firstnames":["Elizabeth"],"suffixes":[]},{"propositions":[],"lastnames":["Malatesta"],"firstnames":["Martina"],"suffixes":[]},{"propositions":[],"lastnames":["Pollen"],"firstnames":["Alex","A"],"suffixes":[]},{"propositions":[],"lastnames":["Nowakowski"],"firstnames":["Tomasz","J"],"suffixes":[]},{"propositions":[],"lastnames":["Kohanbash"],"firstnames":["Gary"],"suffixes":[]},{"propositions":[],"lastnames":["Aghi"],"firstnames":["Manish"],"suffixes":[]},{"propositions":[],"lastnames":["Kriegstein"],"firstnames":["Arnold","R"],"suffixes":[]},{"propositions":[],"lastnames":["Lim"],"firstnames":["Daniel","A"],"suffixes":[]},{"propositions":[],"lastnames":["Diaz"],"firstnames":["Aaron"],"suffixes":[]}],"abstract":"Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in GBM However, clinical trials of tyrosine-kinase inhibitors have shown disappointing efficacy, in part due to intra-tumor heterogeneity. To assess the effect of clonal heterogeneity on gene expression, we derived an approach to map single-cell expression profiles to sequentially acquired mutations identified from exome sequencing. Using 288 single cells, we constructed high-resolution phylogenies of EGF-driven and PDGF-driven GBMs, modeling transcriptional kinetics during tumor evolution. Descending the phylogenetic tree of a PDGF-driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor-like cell type, expressing pro-angiogenic factors. In contrast, phylogenetic analysis of an EGFR-amplified tumor showed an up-regulation of pro-invasive genes. An in-frame deletion in a specific dimerization domain of PDGF receptor correlates with an up-regulation of growth pathways in a proneural GBM and enhances proliferation when ectopically expressed in glioma cell lines. In-frame deletions in this domain are frequent in public GBM data.","journal":"Mol Syst Biol","volume":"12","number":"11","pages":"889","month":"November","year":"2016","keywords":"PDGFRA; copy‐number variation; glioblastoma; single‐cell RNA‐sequencing; tumor phylogeny","language":"en","bibtex":"@ARTICLE{Muller2016-mp,\n title = \"Single-cell sequencing maps gene expression to mutational\n phylogenies in {PDGF-} and {EGF-driven} gliomas\",\n author = \"M{\\\"u}ller, S{\\\"o}ren and Liu, Siyuan John and Di Lullo,\n Elizabeth and Malatesta, Martina and Pollen, Alex A and\n Nowakowski, Tomasz J and Kohanbash, Gary and Aghi, Manish and\n Kriegstein, Arnold R and Lim, Daniel A and Diaz, Aaron\",\n abstract = \"Glioblastoma multiforme (GBM) is the most common and aggressive\n type of primary brain tumor. Epidermal growth factor (EGF) and\n platelet-derived growth factor (PDGF) receptors are frequently\n amplified and/or possess gain-of-function mutations in GBM\n However, clinical trials of tyrosine-kinase inhibitors have shown\n disappointing efficacy, in part due to intra-tumor heterogeneity.\n To assess the effect of clonal heterogeneity on gene expression,\n we derived an approach to map single-cell expression profiles to\n sequentially acquired mutations identified from exome sequencing.\n Using 288 single cells, we constructed high-resolution\n phylogenies of EGF-driven and PDGF-driven GBMs, modeling\n transcriptional kinetics during tumor evolution. Descending the\n phylogenetic tree of a PDGF-driven tumor corresponded to a\n progressive induction of an oligodendrocyte progenitor-like cell\n type, expressing pro-angiogenic factors. In contrast,\n phylogenetic analysis of an EGFR-amplified tumor showed an\n up-regulation of pro-invasive genes. An in-frame deletion in a\n specific dimerization domain of PDGF receptor correlates with an\n up-regulation of growth pathways in a proneural GBM and enhances\n proliferation when ectopically expressed in glioma cell lines.\n In-frame deletions in this domain are frequent in public GBM\n data.\",\n journal = \"Mol Syst Biol\",\n volume = 12,\n number = 11,\n pages = \"889\",\n month = nov,\n year = 2016,\n keywords = \"PDGFRA; copy‐number variation; glioblastoma; single‐cell\n RNA‐sequencing; tumor phylogeny\",\n language = \"en\"\n}\n\n","author_short":["Müller, S.","Liu, S. J.","Di Lullo, E.","Malatesta, M.","Pollen, A. A","Nowakowski, T. J","Kohanbash, G.","Aghi, M.","Kriegstein, A. R","Lim, D. A","Diaz, A."],"key":"Muller2016-mp","id":"Muller2016-mp","bibbaseid":"mller-liu-dilullo-malatesta-pollen-nowakowski-kohanbash-aghi-etal-singlecellsequencingmapsgeneexpressiontomutationalphylogeniesinpdgfandegfdrivengliomas-2016","role":"author","urls":{},"keyword":["PDGFRA; copy‐number variation; glioblastoma; single‐cell RNA‐sequencing; tumor phylogeny"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/f/EJMp3HRuxirjxpcXh/references.bib","dataSources":["sAFYeB74DpbdXM9NN","4zx9n2tbeLTix3Wxr","k3cdWrThyTh5o59Rm","hq9pebjzmsTuyxGGx","h8Atv2SAy4PmShg5j"],"keywords":["pdgfra; copy‐number variation; glioblastoma; single‐cell rna‐sequencing; tumor phylogeny"],"search_terms":["single","cell","sequencing","maps","gene","expression","mutational","phylogenies","pdgf","egf","driven","gliomas","müller","liu","di lullo","malatesta","pollen","nowakowski","kohanbash","aghi","kriegstein","lim","diaz"],"title":"Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas","year":2016}