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学科主题: 临床医学
题名:
A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis
作者: Moriarity, Branden S.1,2,3; Otto, George M.1,2,3,4; Rahrmann, Eric P.1,2,3,4; Rathe, Susan K.; Wolf, Natalie K.4; Weg, Madison T.4; Manlove, Luke A.4; LaRue, Rebecca S.5; Temiz, Nuri A.; Molyneux, Sam D.6; Choi, Kwangmin7; Holly, Kevin J.4; Sarver, Aaron L.; Scott, Milcah C.8; Forster, Colleen L.9; Modiano, Jaime F.8,10; Khanna, Chand11; Hewitt, Stephen M.12; Khokha, Rama6; Yang, Yi13; Gorlick, Richard14,15,16; Dyer, Michael A.17; Largaespada, David A.1,2,3,4
刊名: NATURE GENETICS
发表日期: 2015-06-01
DOI: 10.1038/ng.3293
卷: 47, 期:6, 页:615-624
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
关键词[WOS]: NERVE SHEATH TUMOR ; POOR-PROGNOSIS ; HEPATOCELLULAR-CARCINOMA ; NEUROFIBROMATOSIS TYPE-1 ; CELL-PROLIFERATION ; OSTEOGENIC-SARCOMA ; COLORECTAL-CANCER ; PROSTATE-CANCER ; COPY NUMBER ; EXPRESSION
英文摘要:

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.

语种: 英语
所属项目编号: AR050938 ; 123939 ; R01 CA113636 ; P30 CA077598
项目资助者: US National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases Musculoskeletal Training Grant ; Sobiech Osteosarcoma Fund Award ; Children&prime ; s Cancer Research Fund ; American Cancer Center Research Professor Grant ; National Cancer Institute grant ; comprehensive Masonic Cancer Center (US National Institutes of Health grant)
WOS记录号: WOS:000355386500012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54012
Appears in Collections:北京大学第二临床医学院_骨肿瘤科_期刊论文

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作者单位: 1.Ontario Canc Inst, Toronto, ON M4X 1K9, Canada
2.Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA
3.Univ Minnesota, Ctr Genome Engn, Minneapolis, MN USA
4.Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA
5.Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA
6.Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA
7.Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Hosp Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA
8.Univ Minnesota, Dept Vet Clin Sci, St Paul, MN 55108 USA
9.Univ Minnesota, Acad Hlth Ctr, BioNet, Minneapolis, MN USA
10.Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
11.NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA
12.NCI, TARP, Pathol Lab, Bethesda, MD 20892 USA
13.Peking Univ, Peoples Hosp, Musculoskeletal Tumor Ctr, Dept Orthoped Surg, Beijing 100871, Peoples R China
14.Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA
15.Childrens Hosp Montefiore, Bronx, NY USA
16.Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA
17.St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

Recommended Citation:
Moriarity, Branden S.,Otto, George M.,Rahrmann, Eric P.,et al. A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis[J]. NATURE GENETICS,2015,47(6):615-624.
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