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

doi:10.1186/s13045-014-0076-2

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 journal › Article › peer-review

19 Scopus citations

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 language	English (US)
Article number	76
Journal	Journal of Hematology and Oncology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1186/s13045-014-0076-2
State	Published - Oct 10 2014
Externally published	Yes

Keywords

Fusion gene
KCNMB4-CCND3
LRP1-SNRNP25
Osteosarcoma
Transcriptome sequencing

ASJC Scopus subject areas

Hematology
Molecular Biology
Oncology
Cancer Research

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10.1186/s13045-014-0076-2

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@article{fb66de66974943b190c63926776d2325,

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.",

keywords = "Fusion gene, KCNMB4-CCND3, LRP1-SNRNP25, Osteosarcoma, Transcriptome sequencing",

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

note = "Funding Information: This work was partly supported by the National Nature Science Foundation of China (81372872 to JY, 81402215 to XD and 81320108022 to KC), funds from the University Cancer Foundation via the Sister Institution Network Fund (SINF) (to JY and WZ), the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) in China (IRT1076) (to JY and KC) and the National Key Scientific and Technological Project (2011ZX09307-001-04) (to KC). The tissue bank is jointly supported by a grant from the National Foundation for Cancer Research (US). We are indebted to Wei Tian, Linru Zhao, Yanxue Liu, and Yanrui Zhao for critical technical help. We thank the following individuals for contributing cases or for supplying clinical information: Haixin Li, Jiayong Liu, Jing Chen, Yan Zhang, Huixiang Li, and Yi Pan from Beijing University Cancer Hospital, the first affiliation hospital of Zhengzhou University, and Tianjin Medical University Cancer Hospital. Publisher Copyright: {\textcopyright} 2014 Yang et al.; licensee BioMed Central Ltd.",

year = "2014",

month = oct,

day = "10",

doi = "10.1186/s13045-014-0076-2",

language = "English (US)",

volume = "7",

journal = "Journal of Hematology and Oncology",

issn = "1756-8722",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

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

N1 - Funding Information: This work was partly supported by the National Nature Science Foundation of China (81372872 to JY, 81402215 to XD and 81320108022 to KC), funds from the University Cancer Foundation via the Sister Institution Network Fund (SINF) (to JY and WZ), the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) in China (IRT1076) (to JY and KC) and the National Key Scientific and Technological Project (2011ZX09307-001-04) (to KC). The tissue bank is jointly supported by a grant from the National Foundation for Cancer Research (US). We are indebted to Wei Tian, Linru Zhao, Yanxue Liu, and Yanrui Zhao for critical technical help. We thank the following individuals for contributing cases or for supplying clinical information: Haixin Li, Jiayong Liu, Jing Chen, Yan Zhang, Huixiang Li, and Yi Pan from Beijing University Cancer Hospital, the first affiliation hospital of Zhengzhou University, and Tianjin Medical University Cancer Hospital. Publisher Copyright: © 2014 Yang et al.; licensee BioMed Central Ltd.

PY - 2014/10/10

Y1 - 2014/10/10

N2 - 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.

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

KW - KCNMB4-CCND3

KW - LRP1-SNRNP25

KW - Osteosarcoma

KW - Transcriptome sequencing

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VL - 7

JO - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

SN - 1756-8722

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ER -

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

Abstract

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