Xie Lu, Cai Zhenyu, Lu Hezhe, Meng Fanfei, Zhang Xin, Luo Kun, Su Xiaoxing, Lei Yan, Xu Jiuhui, Lou Jingbing, Wang Han, Du Zhiye, Wang Yunfan, Li Yuan, Ren Tingting, Xu Jie, Sun Xin, Tang Xiaodong, Guo Wei
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China.
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, No. A3 Datun Road, Chaoyang District, Beijing 100101, China.
Heliyon. 2023 Apr 17;9(5):e15527. doi: 10.1016/j.heliyon.2023.e15527. eCollection 2023 May.
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.
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.
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.
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.
与首先转移至肺部的骨肉瘤相比，仅最初转移至骨的骨肉瘤表现出独特的生物学特征，这提示我们其潜在的基因组致病机制不同。
我们分析了38例不同复发模式的骨肉瘤配对样本的全外显子测序（WES）数据。我们还试图基于基因改变重新定义骨肉瘤的疾病亚分类，并将这些基因谱与临床治疗过程相关联，以阐明潜在的进化分支图。
我们研究了38例骨肉瘤患者中的12例（31.6%）高级别骨肉瘤患者的WES，这些患者最初发生骨转移（A组），26例（68.4%）最初发生肺转移（B组），其中15例（39.5%）有原发灶和转移灶的配对样本。我们发现，A组骨肉瘤主要携带单核苷酸变异，显示出更高的肿瘤突变负担和新抗原负荷以及更多的三级淋巴结构，而B组骨肉瘤主要表现为结构变异。在其进化分支图中，随着时间的推移，报告的基因测序具有高度保守性。
主要具有单核苷酸变异而非结构变异的骨肉瘤可能表现出倾向于骨转移的生物学行为以及肿瘤微环境中更好的免疫原性。
