Molecular Characteristics of Osteosarcoma Occurrence and Metastasis Based on High Throughput Sequencing Technology
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0614
- VernacularTitle:基于高通量测序分析骨肉瘤发生和转移的分子特征
- Author:
Ming-xian XU
1
;
Rui-xi LI
2
;
Wei-tang GUO
1
;
Ming-zhe CHENG
1
;
Chang-ye ZOU
1
Author Information
1. Department of Musculoskeletal Oncology， The First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080， China
2. Department of Radiology， The First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
osteosarcoma;
lung metastasis;
NGS;
gene map;
gene mutation
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(6):985-994
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThe purpose of this study was to explore the difference in expression of gene between the osteosarcoma metastasis and primary specimens through NGS detection， in order to find the molecular mechanism of inducing osteosarcoma occurrence and metastasis. MethodsNext generation sequencing （NGS） was used to detect the tumor tissue samples of paired primary and metastatic lesions in 12 patients with metastasis， including 9 pairs of Panel detection （678 genes） and 3 pairs of whole exon detection （WES）. Copy number variation was detected by Excavator. DNA mutations were detected by Lumpy fusion， and RNA mutations were detected with Defuse + Star fusion. The distribution of mutations was shown by Circos. Metascape was used to analyze the enrichment of Go and KEGG signal pathways of differential genes. Pyclone+Citup/LICHEE was used for clonal evolution analysis. ResultsThe most frequent gene mutation mode of osteosarcoma was gene amplification， high-frequency mutation genes were FLCN（37.5%），GID4（37.5%），TP53（33.3%），ATRX（25%），CALR（25%），CCND3（25%），CCNE1（25%），NOCR1（25%），TFEB（25%），VEGFA（25%）， and the mutation frequency of cell cycle pathway was the highest. KT1， PLCG2 and EGFR were closely related to the metastasis of osteosarcoma. The frequency of tumor mutation burden （TMB） in metastatic lesions was significantly higher than primary lesions （P = 0.013）. Three patients detected by WES showed linear clonal evolution， suggesting that the mutations of osteosarcoma metastasis genes may be accumulated sequentially. We identified new candidate genes that may play an important role in the progression of osteosarcoma， including PLCG2， MYO15A and PEX6. ConclusionsThe most frequent gene mutation pattern of osteosarcoma occurrence and metastasis is gene amplification， and the frequency of tumor mutation burden （TMB） in metastatic lesions is significantly higher than that in primary lesions. There is an interrelated linear gene clonal evolution in patients with metastasis. This study suggests that PLCG2， MYO15A and PEX6 may play an important role in the progression of osteosarcoma.
