title: Exomic analysis of myxoid liposarcomas, synovial sarcomas, and osteosarcomas.
abstract: Bone and soft tissue sarcomas are a group of histologically heterogeneous and relatively uncommon tumors. To explore their genetic origins, we sequenced the exomes of 13 osteosarcomas, eight myxoid liposarcomas (MLPS), and seven synovial sarcomas (SYN). These tumors had few genetic alterations (median of 10.8). Nevertheless, clear examples of driver gene mutations were observed, including canonical mutations in TP53, PIK3CA, SETD2, AKT1, and subclonal mutation in FBXW7. Of particular interest were mutations in H3F3A, encoding the variant histone H3.3. Mutations in this gene have only been previously observed in gliomas. Loss of heterozygosity of exomic regions was extensive in osteosarcomas but rare in SYN and MLPS. These results provide intriguing nucleotide-level information on these relatively uncommon neoplasms and highlight pathways that help explain their pathogenesis.
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Joseph
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Heejung
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Isaac
authors.initials: I
authors.lastname: Kinde
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, SE-22185 Lund, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.affiliation: Ministry of Educations Key Laboratory of Clinical Diagnostic Medicine, Chongqinq 400046, China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.affiliation: The University of Chicago Medical Center, Chicago, IL 60637.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, SE-22185 Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.affiliation: Ludwig Center, the Howard Hughes Medical Institutions, and the Departmentof Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics*; D002648:Child; D059472:Exome; D006801:Humans; D018208:Liposarcoma, Myxoid / Q000235:genetics*; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics*; D013584:Sarcoma, Synovial / Q000235:genetics*