Distinct genomic features between osteosarcomas firstly metastasing to bone and to lung
Lu Xie,
Zhenyu Cai,
Hezhe Lu,
Fanfei Meng,
Xin Zhang,
Kun Luo,
Xiaoxing Su,
Yan Lei,
Jiuhui Xu,
Jingbing Lou,
Han Wang,
Zhiye Du,
Yunfan Wang,
Yuan Li,
Tingting Ren,
Jie Xu,
Xin Sun,
Xiaodong Tang,
Wei Guo
Affiliations
Lu Xie
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Zhenyu Cai
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Hezhe Lu
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, No. A3 Datun Road, Chaoyang District, Beijing 100101, China
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Jingbing Lou
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Han Wang
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Zhiye Du
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Yunfan Wang
Pathology Department, Peking University Shougang Hospital, No. 9 Jinyuanzhuang Road, Shijingshan District, Beijing, 100144, China
Yuan Li
Radiology Department & Nuclear Medicine Department, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
Tingting Ren
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Jie Xu
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Xin Sun
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China
Xiaodong Tang
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China; Corresponding author.
Wei Guo
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China; Corresponding author.
Background: Osteosarcoma initially metastasing to bone only shows distinct biological features compared to osteosarcoma that firstly metastasizes to the lung, which suggests us underlying different genomic pathogenetic mechanism. Methods: We analyzed whole-exome sequencing (WES) data for 38 osteosarcoma with paired samples in different relapse patterns. We also sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms. Results: We investigated WES of 12/38 patients with high-grade osteosarcoma (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. We found that osteosarcoma in group A mainly carries single-nucleotide variations displaying higher tumor mutation burden and neoantigen load and more tertiary lymphoid structures, while those in group B mainly exhibits structural variants. High conservation of reported genetic sequencing over time in their evolving cladograms. Conclusions: Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases as well as better immunogenicity in tumor microenvironment.
