69
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Comprehensive molecular characterization of pheochromocytoma and paraganglioma

      research-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 2 , 8 , 9 , 10 , 3 , 3 , 11 , 12 , 13 , 3 , 3 , 6 , 3 , 11 , 14 , 15 , 16 , 17 , The Cancer Genome Atlas Research Network, 18 , 12 , 19 , 3 , 20
      Cancer cell
      pheochromocytoma, paraganglioma, genomics, MAML3, CSDE1, sequencing, expression subtypes, TCGA, molecular profiling, metastasis

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCC/PGLs), a rare tumor type. Multi-platform integration revealed that PCC/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically-mutated driver gene, complementing four known drivers ( HRAS, RET, EPAS1, NF1). We also discovered fusion genes in PCC/PGL, involving MAML3, BRAF, NGFR and NF1. Integrated analysis classified PCC/PGLs into four molecularly-defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCC/PGL included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

          Graphical abstract

          Related collections

          Author and article information

          Journal
          101130617
          29778
          Cancer Cell
          Cancer Cell
          Cancer cell
          1535-6108
          1878-3686
          2 May 2017
          02 February 2017
          13 February 2017
          13 February 2018
          : 31
          : 2
          : 181-193
          Affiliations
          [1 ]Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 USA
          [2 ]The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142 USA
          [3 ]Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
          [4 ]The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21287 USA
          [5 ]Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6 Canada
          [6 ]Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
          [7 ]The Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205 USA
          [8 ]Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610 USA
          [9 ]Division of Metabolism, Endocrinology, & Diabetes, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA
          [10 ]University of Texas MD Anderson Cancer Center Houston, TX, 77030, USA
          [11 ]Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
          [12 ]Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 USA
          [13 ]Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
          [14 ]INSERM, UMR970, Paris-Cardiovascular Research Center, F-75015, Paris, France
          [15 ]Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109, USA
          [16 ]Department of Pathology, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 2C4 Canada
          [17 ]Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston MA 02111 USA
          [18 ]Endocrinology and Tumor Genetics Affinity Group, Eunice Kennedy Shriver NICHD, NIH MD 20892 USA
          [19 ]Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 USA
          [20 ]Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
          Author notes
          [* ]Corresponding authors: Matthew D. Wilkerson: mdwilkerson@ 123456outlook.com ; Katherine L. Nathanson: knathans@ 123456exchange.upenn.edu ; Karel Pacak: karel@ 123456mail.nih.gov
          [†]

          Co-first authors

          [a]

          Lead Contact

          [‡]

          Current address: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA

          [§]

          Current address: Division of Hematology and Oncology, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

          [ᵟ]

          Current address: The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA

          Article
          PMC5643159 PMC5643159 5643159 nihpa849815
          10.1016/j.ccell.2017.01.001
          5643159
          28162975
          5c17d620-d362-4dfe-b60f-a1a71c95dd84
          History
          Categories
          Article

          pheochromocytoma,paraganglioma,genomics,MAML3,CSDE1,sequencing,expression subtypes,TCGA,molecular profiling,metastasis

          Comments

          Comment on this article

          Related Documents Log