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 | |
| State | Published - Oct 10 2014 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=84907933570&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907933570&partnerID=8YFLogxK
U2 - 10.1186/s13045-014-0076-2
DO - 10.1186/s13045-014-0076-2
M3 - Article
C2 - 25300797
AN - SCOPUS:84907933570
VL - 7
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
SN - 1756-8722
IS - 1
M1 - 76
ER -