Clinical Research
Osteosarcoma with bone metastasis or pulmonary metastasis show distinct genomic manifestations
Cai Zhenyu, She Yanchun, Xie Lu, Wang Han, Du Zhiye, Li Yuan, Ren Tingting, Xu Jie, Sun Xin, Sun Kunkun, Shen Danhua, Tang Xiaodong, Guo Wei
Published 2023-05-01
Cite as Chin J Orthop, 2023, 43(9): 581-590. DOI: 10.3760/cma.j.cn121113-20220915-00543
Abstract
ObjectiveTo investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.
MethodsFrom May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We 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.
ResultsWe found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group (P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms.
ConclusionOsteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.
Key words:
Osteosarcoma; Neoplasm metastasis; Genomics; Genomic structural variation; Single-nucleotide variation
Contributor Information
Cai Zhenyu
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
She Yanchun
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
Xie Lu
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
Wang Han
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
Du Zhiye
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
Li Yuan
Department of Nuclear Medicine, Peking Uiversity People's Hospital, Beijing 100044, China
Ren Tingting
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
Xu Jie
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
Sun Xin
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
Sun Kunkun
Department of Tathology, Peking University People's Hospital, Beijing 100044, China
Shen Danhua
Department of Tathology, Peking University People's Hospital, Beijing 100044, China
Tang Xiaodong
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
Guo Wei
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China
