Whole-exome sequencing in osteosarcoma with distinct prognosis reveals disparate genetic heterogeneity.

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.