title: Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma.
abstract: BACKGROUND
  The identification of fusion genes such as SYT-SSX1/SSX2, PAX3-FOXO1, TPM3/TPM4-ALK and EWS-FLI1 in human sarcomas has provided important insight into the diagnosis and targeted therapy of sarcomas. No recurrent fusion has been reported in human osteosarcoma.
  
  
  METHODS
  Transcriptome sequencing was used to characterize the gene fusions and mutations in 11 human osteosarcomas.
  
  
  RESULTS
  Nine of 11 samples were found to harbor genetic inactivating alterations in the TP53 pathway. Two recurrent fusion genes associated with the 12q locus, LRP1-SNRNP25 and KCNMB4-CCND3, were identified and validated by RT-PCR, Sanger sequencing and fluorescence in situ hybridization, and were found to be osteosarcoma specific in a validation cohort of 240 other sarcomas. Expression of LRP1-SNRNP25 fusion gene promoted SAOS-2 osteosarcoma cell migration and invasion. Expression of KCNMB4-CCND3 fusion gene promoted SAOS-2 cell migration.
  
  
  CONCLUSIONS
  Our study represents the first whole transcriptome analysis of untreated human osteosarcoma. Our discovery of two osteosarcoma specific fusion genes associated with osteosarcoma cellular motility highlights the heterogeneity of osteosarcoma and provides opportunities for new treatment modalities.
authors.affiliation: Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Hospital & Institute, Tianjin, 30060, PR China. yangjilong@tjmuch.com.|National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, PR China. yangjilong@tjmuch.com.
authors.forename: Jilong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Signal Processing, Tampere University of Technology, Tampere, 33101, Finland. matti.annala@tut.fi.|Institute of Biomedical Technology, University of Tampere, Tampere, 33520, Finland. matti.annala@tut.fi.
authors.forename: Matti
authors.initials: M
authors.lastname: Annala
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. pji@mdanderson.org.
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.affiliation: Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Hospital & Institute, Tianjin, 30060, PR China. wgwhrb@163.com.|National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, PR China. wgwhrb@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital & Institute, Tianjin, 30060, PR China. zhengh64@aliyun.com.|National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, PR China. zhengh64@aliyun.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. dcogdell@mdanderson.org.
authors.forename: David
authors.initials: D
authors.lastname: Codgell
authors.affiliation: Department of Diagnostics, Tianjin Medical University, Tianjin, 30060, PR China. xiaolingdu2003@163.com.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Bone and Soft Tissue Tumors, Beijing University Cancer Hospital, Beijing, 100020, PR China. fzhiwei66@163.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Hospital & Institute, Tianjin, 30060, PR China. sunbaocun@tjmuch.com.|National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, PR China. sunbaocun@tjmuch.com.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Signal Processing, Tampere University of Technology, Tampere, 33101, Finland. matti.nykter@tut.fi.
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
authors.affiliation: Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital & Institute, Tianjin, 30060, PR China. chenkexin1963@yahoo.com.|National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, PR China. chenkexin1963@yahoo.com.
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. wzhang@mdanderson.org.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics*; D015331:Cohort Studies; D056743:Cyclin D3 / Q000235:genetics*; D005260:Female; D050939:Gene Fusion; D006801:Humans; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000235:genetics*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics*; D059467:Transcriptome; D055815:Young Adult
chemical_list: C534696:CCND3 protein, human; D056743:Cyclin D3; C410183:KCNMB4 protein, human; C475476:LRP1 protein, human; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009419:Nerve Tissue Proteins; D017411:Ribonucleoproteins, Small Nuclear; C552138:SNRNP25 protein, human