The correlation between clinical outcomes and genomic analysis with high risk factors for the progression of osteosarcoma
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies..
Osteosarcoma (OS) is a rare but aggressive malignancy. Despite previous reports, molecular characterization of this disease is not well understood, and little is known regarding OS in Chinese patients. Herein, we analyzed the genomic signatures of 73 Chinese OS cases. TP53, NCOR1, LRP1B, ATRX, RB1, and TFE3 were the most frequently mutated gene in our OS cohort. In addition, the genomic analysis of Western OS patients was performed. Notably, there were remarkable disparities in mutational landscape, base substitution pattern, and tumor mutational burden between the Chinese and Western OS cohorts. Specific molecular mechanisms, including DNA damage repair (DDR) gene mutations, copy number variation (CNV) presence, aneuploidy, and intratumoral heterogeneity, were associated with disease progression. Additionally, 30.1% of OS patients carried clinically actionable alterations, which were mainly enriched in PI3K, MAPK, DDR, and RTK signaling pathways. A specific molecular subtype incorporating DDR alterations and CNVs was significantly correlated with distant metastasis-free survival and event-free survival, and this correlation was observed in all subgroups with different characteristics. These findings comprehensively elucidated the genomic profile and revealed novel prognostic factors in OS, which would contribute to understanding this disease and promoting precision medicine of this population.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Molecular oncology - 18(2024), 4 vom: 12. Apr., Seite 939-955 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Weifeng [VerfasserIn] |
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| Links: |
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| Themen: |
Actionable mutation profile |
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| Anmerkungen: |
Date Completed 05.04.2024 Date Revised 06.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/1878-0261.13526 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM362239428 |
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| 520 | |a Osteosarcoma (OS) is a rare but aggressive malignancy. Despite previous reports, molecular characterization of this disease is not well understood, and little is known regarding OS in Chinese patients. Herein, we analyzed the genomic signatures of 73 Chinese OS cases. TP53, NCOR1, LRP1B, ATRX, RB1, and TFE3 were the most frequently mutated gene in our OS cohort. In addition, the genomic analysis of Western OS patients was performed. Notably, there were remarkable disparities in mutational landscape, base substitution pattern, and tumor mutational burden between the Chinese and Western OS cohorts. Specific molecular mechanisms, including DNA damage repair (DDR) gene mutations, copy number variation (CNV) presence, aneuploidy, and intratumoral heterogeneity, were associated with disease progression. Additionally, 30.1% of OS patients carried clinically actionable alterations, which were mainly enriched in PI3K, MAPK, DDR, and RTK signaling pathways. A specific molecular subtype incorporating DDR alterations and CNVs was significantly correlated with distant metastasis-free survival and event-free survival, and this correlation was observed in all subgroups with different characteristics. These findings comprehensively elucidated the genomic profile and revealed novel prognostic factors in OS, which would contribute to understanding this disease and promoting precision medicine of this population | ||
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| 650 | 4 | |a disease progression | |
| 650 | 4 | |a molecular characterization | |
| 650 | 4 | |a osteosarcoma | |
| 650 | 4 | |a risk factors | |
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| 700 | 1 | |a Huang, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yaping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanrui |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yongkun |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Zhiping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Lou, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Shanbo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Huina |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Xiaohui |e verfasserin |4 aut | |
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