Your browser doesn't support javascript.
loading
A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis.
Moriarity, Branden S; Otto, George M; Rahrmann, Eric P; Rathe, Susan K; Wolf, Natalie K; Weg, Madison T; Manlove, Luke A; LaRue, Rebecca S; Temiz, Nuri A; Molyneux, Sam D; Choi, Kwangmin; Holly, Kevin J; Sarver, Aaron L; Scott, Milcah C; Forster, Colleen L; Modiano, Jaime F; Khanna, Chand; Hewitt, Stephen M; Khokha, Rama; Yang, Yi; Gorlick, Richard; Dyer, Michael A; Largaespada, David A.
Afiliação
  • Moriarity BS; 1] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. [2] Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA. [3] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
  • Otto GM; 1] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. [2] Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA. [3] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [4] Department of Genetics, Cell Biology and De
  • Rahrmann EP; 1] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. [2] Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA. [3] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [4] Department of Genetics, Cell Biology and De
  • Rathe SK; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
  • Wolf NK; 1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
  • Weg MT; 1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
  • Manlove LA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
  • LaRue RS; 1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  • Temiz NA; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
  • Molyneux SD; Ontario Cancer Institute, Toronto, Ontario, Canada.
  • Choi K; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
  • Holly KJ; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
  • Sarver AL; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
  • Scott MC; 1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, Minnesota, USA.
  • Forster CL; BioNet, Academic Health Center, University of Minnesota, Minneapolis, Minnesota, USA.
  • Modiano JF; 1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, Minnesota, USA. [3] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Khanna C; Tumor and Metastasis Biology Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
  • Hewitt SM; Tissue Array Research Program (TARP), Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
  • Khokha R; Ontario Cancer Institute, Toronto, Ontario, Canada.
  • Yang Y; Department of Orthopedic Surgery, Musculoskeletal Tumor Center, People's Hospital, Peking University, Beijing, China.
  • Gorlick R; 1] Department of Pediatrics, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York, USA. [2] Department of Molecular Pharmacology, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York, USA.
  • Dyer MA; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Largaespada DA; 1] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. [2] Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA. [3] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [4] Department of Genetics, Cell Biology and De
Nat Genet ; 47(6): 615-24, 2015 Jun.
Article em En | MEDLINE | ID: mdl-25961939
ABSTRACT
Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Osteossarcoma Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Osteossarcoma Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article