title: Werner syndrome through the lens of tissue and tumour genomics.
abstract: Werner syndrome (WS) is the canonical adult human progeroid ('premature aging') syndrome. Patients with this autosomal recessive Mendelian disorder display constitutional genomic instability and an elevated risk of important age-associated diseases including cancer. Remarkably few analyses of WS patient tissue and tumors have been performed to provide insight into WS disease pathogenesis or the high risk of neoplasia. We used autopsy tissue from four mutation-typed WS patients to characterize pathologic and genomic features of WS, and to determine genomic features of three neoplasms arising in two of these patients. The results of these analyses provide new information on WS pathology and genomics; provide a first genomic characterization of neoplasms arising in WS; and provide new histopathologic and genomic data to test several popular models of WS disease pathogenesis.
authors: Department of Medicine Division of Medical Genetics, University of Washington, Seattle, WA USA.
authors: Mari
authors: M
authors: Tokita
authors: Department of Pathology, University of Washington, Seattle, WA USA.
authors: Scott R
authors: SR
authors: Kennedy
authors: Department of Pathology, University of Washington, Seattle, WA USA.
authors: Rosa Ana
authors: RA
authors: Risques
authors: Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX USA.
authors: Stephen G
authors: SG
authors: Chun
authors: Department of Laboratory Medicine, University of Washington, Seattle, WA USA.
authors: Colin
authors: C
authors: Pritchard
authors: Department of Pathology, University of Washington, Seattle, WA USA.|Department of Medicine, Chiba University, Chiba, Japan.
authors: Junko
authors: J
authors: Oshima
authors: Department of Pathology, University of Washington, Seattle, WA USA.
authors: Yan
authors: Y
authors: Liu
authors: Department of Pathology, John Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI USA.
authors: Peter K
authors: PK
authors: Bryant-Greenwood
authors: Department of Pathology, University of Washington, Seattle, WA USA.
authors: Piri
authors: P
authors: Welcsh
authors: Department of Pathology, University of Washington, Seattle, WA USA.|Department of Genome Sciences, University of Washington, Seattle, WA USA.
authors: Raymond J
authors: RJ
authors: Monnat
mesh_terms: D000328:Adult; D016922:Cellular Senescence; D004272:DNA, Mitochondrial; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D016615:Telomere / Q000235:genetics; D014898:Werner Syndrome / Q000235:genetics* / Q000473:pathology*; D000071657:Werner Syndrome Helicase / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase