The genomic profiles of osteosarcoma (OS) patients have been extensively investigated; however, the genetic prognostic biomarkers still remain unclear. In the present study, we analyzed the mutational profiles of pre-treatment primary tumor samples from 33 OS patients using whole exome sequencing (WES). These 33 OS patients were divided into two groups according to clinical outcomes: a good prognosis group involving 21 patients with tumor free survival, and a poor prognosis group involving the remaining12 patients who had lung metastases at initial diagnosis. Overall we found that the MAPK signaling pathway may play an important role in determining a good prognosis, while the PI3K-Akt signaling pathway may be an important factor leading to a poor prognosis. Significant differences were observed in the number of somatic copy number alterations, including del (3p), amp (4q), del (7p) and amp (8q), between the two groups. Moreover, significant differences were observed in mutation sites and frequencies between these two groups. The good prognosis group exhibited a significantly higher mutation frequency in somatic JAK-STAT and germline base excision repair pathways than the poor prognosis group. Furthermore, significant difference was also observed in the frequency of potentially actionable alterations between the two groups, suggesting that patients with a poor prognosis potentially have access to a larger number of treatment options. These findings highlight the importance of evaluating genomic disparities in OS, and provide a novel insight into the potential prognostic biomarkers.

骨肉瘤 (OS) 患者的基因组谱已被广泛研究；然而，遗传预后生物标志物仍不清楚。在本研究中，我们使用全外显子组测序（WES）分析了来自 33 名 OS 患者的治疗前原发性肿瘤样本的突变谱。这 33 名 OS 患者根据临床结果分为两组：预后良好组包括 21 名无瘤生存患者，预后不良组包括其余 12 名初诊时有肺转移的患者。总体而言，我们发现 MAPK 信号通路可能在决定良好预后方面发挥重要作用，而 PI3K-Akt 信号通路可能是导致不良预后的重要因素。在体细胞拷贝数改变的数量上观察到显着差异，包括del（3p）、amp（4q）、del（7p）和amp（8q），介于两组之间。此外，在这两组之间观察到突变位点和频率的显着差异。与预后不良组相比，预后良好组在体细胞 JAK-STAT 和种系碱基切除修复途径中表现出显着更高的突变频率。此外，还观察到两组之间潜在可操作改变的频率存在显着差异，这表明预后不良的患者可能有更多的治疗选择。这些发现强调了评估 OS 中基因组差异的重要性，并为潜在的预后生物标志物提供了新的见解。在这两组之间观察到突变位点和频率的显着差异。与预后不良组相比，预后良好组在体细胞 JAK-STAT 和种系碱基切除修复途径中表现出显着更高的突变频率。此外，还观察到两组之间潜在可操作改变的频率存在显着差异，这表明预后不良的患者可能有更多的治疗选择。这些发现强调了评估 OS 中基因组差异的重要性，并为潜在的预后生物标志物提供了新的见解。在这两组之间观察到突变位点和频率的显着差异。与预后不良组相比，预后良好组在体细胞 JAK-STAT 和种系碱基切除修复途径中表现出显着更高的突变频率。此外，还观察到两组之间潜在可操作改变的频率存在显着差异，这表明预后不良的患者可能有更多的治疗选择。这些发现强调了评估 OS 中基因组差异的重要性，并为潜在的预后生物标志物提供了新的见解。与预后不良组相比，预后良好组在体细胞 JAK-STAT 和种系碱基切除修复途径中表现出显着更高的突变频率。此外，还观察到两组之间潜在可操作改变的频率存在显着差异，这表明预后不良的患者可能有更多的治疗选择。这些发现强调了评估 OS 中基因组差异的重要性，并为潜在的预后生物标志物提供了新的见解。与预后不良组相比，预后良好组在体细胞 JAK-STAT 和种系碱基切除修复途径中表现出显着更高的突变频率。此外，还观察到两组之间潜在可操作改变的频率存在显着差异，这表明预后不良的患者可能有更多的治疗选择。这些发现强调了评估 OS 中基因组差异的重要性，并为潜在的预后生物标志物提供了新的见解。