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Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs.
Hadi, Kevin; Yao, Xiaotong; Behr, Julie M; Deshpande, Aditya; Xanthopoulakis, Charalampos; Tian, Huasong; Kudman, Sarah; Rosiene, Joel; Darmofal, Madison; DeRose, Joseph; Mortensen, Rick; Adney, Emily M; Shaiber, Alon; Gajic, Zoran; Sigouros, Michael; Eng, Kenneth; Wala, Jeremiah A; Wrzeszczynski, Kazimierz O; Arora, Kanika; Shah, Minita; Emde, Anne-Katrin; Felice, Vanessa; Frank, Mayu O; Darnell, Robert B; Ghandi, Mahmoud; Huang, Franklin; Dewhurst, Sally; Maciejowski, John; de Lange, Titia; Setton, Jeremy; Riaz, Nadeem; Reis-Filho, Jorge S; Powell, Simon; Knowles, David A; Reznik, Ed; Mishra, Bud; Beroukhim, Rameen; Zody, Michael C; Robine, Nicolas; Oman, Kenji M; Sanchez, Carissa A; Kuhner, Mary K; Smith, Lucian P; Galipeau, Patricia C; Paulson, Thomas G; Reid, Brian J; Li, Xiaohong; Wilkes, David; Sboner, Andrea; Mosquera, Juan Miguel.
Affiliation
  • Hadi K; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA.
  • Yao X; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA; Tri-institutional PhD Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Behr JM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA; Tri-institutional PhD Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Deshpande A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA; Tri-institutional PhD Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Xanthopoulakis C; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Tian H; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA.
  • Kudman S; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Rosiene J; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA.
  • Darmofal M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA; Tri-institutional PhD Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • DeRose J; New York Genome Center, New York, NY 10013, USA.
  • Mortensen R; New York Genome Center, New York, NY 10013, USA.
  • Adney EM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA.
  • Shaiber A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; New York Genome Center, New York, NY 10013, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Gajic Z; New York Genome Center, New York, NY 10013, USA.
  • Sigouros M; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Eng K; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Wala JA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Wrzeszczynski KO; New York Genome Center, New York, NY 10013, USA.
  • Arora K; New York Genome Center, New York, NY 10013, USA.
  • Shah M; New York Genome Center, New York, NY 10013, USA.
  • Emde AK; New York Genome Center, New York, NY 10013, USA.
  • Felice V; New York Genome Center, New York, NY 10013, USA.
  • Frank MO; New York Genome Center, New York, NY 10013, USA; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Darnell RB; New York Genome Center, New York, NY 10013, USA; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Ghandi M; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Huang F; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Dewhurst S; Laboratory of Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USA.
  • Maciejowski J; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • de Lange T; Laboratory of Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USA.
  • Setton J; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Riaz N; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New Yor
  • Reis-Filho JS; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Powell S; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Knowles DA; New York Genome Center, New York, NY 10013, USA; Department of Computer Science, Columbia University, New York, NY 10027, USA.
  • Reznik E; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Mishra B; Departments of Computer Science, Mathematics and Cell Biology, Courant Institute and NYU School of Medicine, New York University, New York, NY 10012, USA.
  • Beroukhim R; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Zody MC; New York Genome Center, New York, NY 10013, USA.
  • Robine N; New York Genome Center, New York, NY 10013, USA.
  • Oman KM; Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Sanchez CA; Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Kuhner MK; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
  • Smith LP; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
  • Galipeau PC; Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Paulson TG; Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Reid BJ; Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
  • Li X; Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Wilkes D; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Sboner A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Mosquera JM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Cell ; 183(1): 197-210.e32, 2020 10 01.
Article in En | MEDLINE | ID: mdl-33007263
ABSTRACT
Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.g., chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole-genome sequences, we uncovered three novel complex rearrangement phenomena pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early-replicating regions, superenhancers, and breast or ovarian cancers. Rigma comprise "chasms" of low-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold-back inversions associated with expressed protein-coding fusions, breakend hypermutation, and acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis.
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Full text: 1 Database: MEDLINE Main subject: Genomics / Genomic Structural Variation / Neoplasms Limits: Humans Language: En Journal: Cell Year: 2020 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Genomics / Genomic Structural Variation / Neoplasms Limits: Humans Language: En Journal: Cell Year: 2020 Type: Article Affiliation country: United States