Abstract 1507P
Background
Osteosarcoma (OS) initially metastasing to bone only shows distinct biological features compared to osteosarcoma that initially metastasizes to the lung, which suggests an underlying difference in genomic pathogenetic mechanism. However, related studies are lacking.
Methods
We analyzed whole-exome sequencing (WES) data for 38 metastatic OS patients with different relapse patterns. Multiplex Immunohistochemistry was also applied to investigate the immune- microenvironment. We tried to redefine disease subclassifications for OS based on genetic alterations to guide treatment strategies, and we correlated these genetic profiles with clinical treatment courses and prognosis to elucidate potential evolving cladograms.
Results
We investigated whole-exome sequencing of 12/38 patients with high-grade OS (31.6%) with initial bone metastasis (group A) and 26/38 (68.4%) with initial pulmonary metastasis (group B), of whom 15/38 (39.5%) had paired samples of primary lesions and metastatic lesions for these two cohorts with different relapse patterns. We found that osteosarcoma in group A mainly carries single-nucleotide variations while those in group B mainly exhibits structural variants. Additionally, osteosarcoma in group A displayed better immunogenicity, including a higher tumor mutation burden and neoantigen load and more tertiary lymphoid structures in tumor microenvironment. Table: 1507P
The difference of osteosarcoma patients’ genomic alterations between group A and group B
| Group A | Group B | Statistical method | p value | |
| n (%) | 12 (31.6) | 26 (68.4) | ||
| Genomic type, n (%) | Chi-square | 0.0180a | ||
| SNV | 10 (26.3) | 11 (28.9) | ||
| SV or mixed | 2 (5.3) | 15 (39.5) | ||
| TMB | Wilcoxon | 0.0100a | ||
| Range | 1.1-32.9 | 0-14.2 | ||
| Median (Q1, Q3) | 4.85 (2.75, 11.98) | 2.4 (1.38, 4.45) | ||
| Neoantigen | Wilcoxon | 0.002∗ | ||
| Range | 57-2084 | 0-1539 | ||
| Median (Q1, Q3) | 743 (316.5, 1034.5) | 128.5 (49, 200.5) | ||
| MSI, n (%) | Chi-square | 0.3160 | ||
| MSS | 11 (29.0) | 26 (68.4) | ||
| MSI-H | 1 (2.6) | 0 (0.0) | ||
| HED-status, n (%) | Chi-square | 1.0000 | ||
| Low | 10 (26.3) | 22 (57.9) | ||
| High | 2 (5.3) | 4 (10.5) |
Conclusions
Osteosarcoma with different relapse patterns has distinct genomic landscapes. This study suggests that osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases; immunotherapy is a promising therapeutic option for this group of patients.
Clinical trial identification
This trial was registered in the Medical Ethics Committee of Peking University People’s Hospital on June 25th, 2019 (Institutional Review Board, IRB, number of 2019PHB139-01). NCT03997747.
Editorial acknowledgement
No, we did not have any editorial assistance.
Legal entity responsible for the study
The author.
Funding
Chinese National Natural Science Foundation.
Disclosure
The author has declared no conflicts of interest.