Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs.

Autor:	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., Wrzeszczyński 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 York, NY 10065, USA., 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., Elemento O; 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., Imielinski M; 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; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: mski@mskilab.org.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2020 Oct 01; Vol. 183 (1), pp. 197-210.e32.
DOI:	10.1016/j.cell.2020.08.006
Abstrakt:	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. Competing Interests: Declaration of Interests J.S.R.-F. reports receiving personal/consultancy fees from VolitionRx, Paige.AI, Goldman Sachs, REPARE Therapeutics, GRAIL, Ventana Medical Systems, Roche, Genentech, and InviCRO outside of the scope of the submitted work. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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