Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma

Jilong Yang, Matti Annala, Ping Ji, Guowen Wang, Hong Zheng, David Codgell, Xiaoling Du, Zhiwei Fang, Baocun Sun, Matti Nykter, Kexin Chen, Wei Zhang

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article number76
JournalJournal of Hematology and Oncology
Volume7
Issue number1
DOIs
StatePublished - Oct 10 2014
Externally publishedYes

Fingerprint

Gene Fusion
Osteosarcoma
Cell Movement
Neoplasms
Sarcoma
Gene Expression Profiling
Fluorescence In Situ Hybridization
Transcriptome
Polymerase Chain Reaction
Mutation

Keywords

  • Fusion gene
  • KCNMB4-CCND3
  • LRP1-SNRNP25
  • Osteosarcoma
  • Transcriptome sequencing

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Molecular Biology
  • Medicine(all)

Cite this

Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma. / Yang, Jilong; Annala, Matti; Ji, Ping; Wang, Guowen; Zheng, Hong; Codgell, David; Du, Xiaoling; Fang, Zhiwei; Sun, Baocun; Nykter, Matti; Chen, Kexin; Zhang, Wei.

In: Journal of Hematology and Oncology, Vol. 7, No. 1, 76, 10.10.2014.

Research output: Contribution to journalArticle

Yang, J, Annala, M, Ji, P, Wang, G, Zheng, H, Codgell, D, Du, X, Fang, Z, Sun, B, Nykter, M, Chen, K & Zhang, W 2014, 'Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma', Journal of Hematology and Oncology, vol. 7, no. 1, 76. https://doi.org/10.1186/s13045-014-0076-2
Yang, Jilong ; Annala, Matti ; Ji, Ping ; Wang, Guowen ; Zheng, Hong ; Codgell, David ; Du, Xiaoling ; Fang, Zhiwei ; Sun, Baocun ; Nykter, Matti ; Chen, Kexin ; Zhang, Wei. / Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma. In: Journal of Hematology and Oncology. 2014 ; Vol. 7, No. 1.
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T1 - Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma

AU - Yang, Jilong

AU - Annala, Matti

AU - Ji, Ping

AU - Wang, Guowen

AU - Zheng, Hong

AU - Codgell, David

AU - Du, Xiaoling

AU - Fang, Zhiwei

AU - Sun, Baocun

AU - Nykter, Matti

AU - Chen, Kexin

AU - Zhang, Wei

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AB - 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.

KW - Fusion gene

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KW - Transcriptome sequencing

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