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Open Access 01-12-2014 | Research

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

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

Published in: Journal of Hematology & Oncology | Issue 1/2014

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.

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Title: Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma
Authors: Jilong Yang
Matti Annala
Ping Ji
Guowen Wang
Hong Zheng
David Codgell
Xiaoling Du
Zhiwei Fang
Baocun Sun
Matti Nykter
Kexin Chen
Wei Zhang
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-014-0076-2

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