IR@PKUHSC  > 北京大学第二临床医学院  > 骨肿瘤科
学科主题临床医学
A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis
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
2015-06-01
DOI10.1038/ng.3293
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
WOS记录号WOS:000355386500012
项目编号AR050938 ; 123939 ; R01 CA113636 ; P30 CA077598
资助机构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)
引用统计
被引频次:67[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54012
专题北京大学第二临床医学院_骨肿瘤科
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
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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.
APA Moriarity, Branden S..,Otto, George M..,Rahrmann, Eric P..,Rathe, Susan K..,Wolf, Natalie K..,...&Largaespada, David A..(2015).A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis.NATURE GENETICS,47(6),615-624.
MLA Moriarity, Branden S.,et al."A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis".NATURE GENETICS 47.6(2015):615-624.
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