Your browser doesn't support javascript.
loading
Interpretation of cancer mutations using a multiscale map of protein systems.
Zheng, Fan; Kelly, Marcus R; Ramms, Dana J; Heintschel, Marissa L; Tao, Kai; Tutuncuoglu, Beril; Lee, John J; Ono, Keiichiro; Foussard, Helene; Chen, Michael; Herrington, Kari A; Silva, Erica; Liu, Sophie N; Chen, Jing; Churas, Christopher; Wilson, Nicholas; Kratz, Anton; Pillich, Rudolf T; Patel, Devin N; Park, Jisoo; Kuenzi, Brent; Yu, Michael K; Licon, Katherine; Pratt, Dexter; Kreisberg, Jason F; Kim, Minkyu; Swaney, Danielle L; Nan, Xiaolin; Fraley, Stephanie I; Gutkind, J Silvio; Krogan, Nevan J; Ideker, Trey.
Affiliation
  • Zheng F; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Kelly MR; Cancer Cell Map Initiative (CCMI), La Jolla, CA, USA.
  • Ramms DJ; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Heintschel ML; Cancer Cell Map Initiative (CCMI), La Jolla, CA, USA.
  • Tao K; Cancer Cell Map Initiative (CCMI), La Jolla, CA, USA.
  • Tutuncuoglu B; Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
  • Lee JJ; Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA.
  • Ono K; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
  • Foussard H; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239, USA.
  • Chen M; Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97201, USA.
  • Herrington KA; Cancer Cell Map Initiative (CCMI), La Jolla, CA, USA.
  • Silva E; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Liu SN; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Chen J; Quantitative Biosciences Institute, University of California, San Francisco, CA 94158, USA.
  • Churas C; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Wilson N; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Kratz A; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Pillich RT; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Patel DN; Quantitative Biosciences Institute, University of California, San Francisco, CA 94158, USA.
  • Park J; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Kuenzi B; Department of Biochemistry and Biophysics Center for Advanced Light Microscopy at UCSF, University of California, San Francisco, CA 94158, USA.
  • Yu MK; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Licon K; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Pratt D; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Kreisberg JF; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Kim M; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Swaney DL; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Nan X; Cancer Cell Map Initiative (CCMI), La Jolla, CA, USA.
  • Fraley SI; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Gutkind JS; Cancer Cell Map Initiative (CCMI), La Jolla, CA, USA.
  • Krogan NJ; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Ideker T; Cancer Cell Map Initiative (CCMI), La Jolla, CA, USA.
Science ; 374(6563): eabf3067, 2021 Oct.
Article in En | MEDLINE | ID: mdl-34591613
A major goal of cancer research is to understand how mutations distributed across diverse genes affect common cellular systems, including multiprotein complexes and assemblies. Two challenges­how to comprehensively map such systems and how to identify which are under mutational selection­have hindered this understanding. Accordingly, we created a comprehensive map of cancer protein systems integrating both new and published multi-omic interaction data at multiple scales of analysis. We then developed a unified statistical model that pinpoints 395 specific systems under mutational selection across 13 cancer types. This map, called NeST (Nested Systems in Tumors), incorporates canonical processes and notable discoveries, including a PIK3CA-actomyosin complex that inhibits phosphatidylinositol 3-kinase signaling and recurrent mutations in collagen complexes that promote tumor proliferation. These systems can be used as clinical biomarkers and implicate a total of 548 genes in cancer evolution and progression. This work shows how disparate tumor mutations converge on protein assemblies at different scales.
Subject(s)
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Interaction Maps / Neoplasm Proteins / Neoplasms Limits: Humans Language: En Journal: Science Year: 2021 Document type: Article Affiliation country: Country of publication:
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Interaction Maps / Neoplasm Proteins / Neoplasms Limits: Humans Language: En Journal: Science Year: 2021 Document type: Article Affiliation country: Country of publication: