Comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomas
IntroductionSarcomas are classified into two types, bone sarcoma and soft tissue sarcoma (STS), which account for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. There exist more than 50 subtypes within the two types of sarcoma. Each subtype is highly diverse an...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1173275/full |
| _version_ | 1797774934086254592 |
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| author | Qing Zhang Yongkun Yang Xia You Xia You Xia You Yongzhi Ju Yongzhi Ju Yongzhi Ju Qin Zhang Qin Zhang Qin Zhang Tingting Sun Tingting Sun Tingting Sun Weifeng Liu |
| author_facet | Qing Zhang Yongkun Yang Xia You Xia You Xia You Yongzhi Ju Yongzhi Ju Yongzhi Ju Qin Zhang Qin Zhang Qin Zhang Tingting Sun Tingting Sun Tingting Sun Weifeng Liu |
| author_sort | Qing Zhang |
| collection | DOAJ |
| description | IntroductionSarcomas are classified into two types, bone sarcoma and soft tissue sarcoma (STS), which account for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. There exist more than 50 subtypes within the two types of sarcoma. Each subtype is highly diverse and characterized by significant variations in morphology and phenotypes. Understanding tumor molecular genetics is helpful in improving the diagnostic accuracy of tumors that have been difficult to classify based on morphology alone or that have overlapping morphological features. The different molecular characteristics of bone sarcoma and STS in China remain poorly understood. Therefore, this study aimed to analyze genomic landscapes and actionable genomic alterations (GAs) as well as tumor mutational burden (TMB), microsatellite instability (MSI), and programmed death ligand-1 (PD-L1) expression among Chinese individuals diagnosed with primary bone sarcomas and STS.MethodsThis retrospective study included 145 patients with primary bone sarcomas (n = 75) and STS (n = 70), who were categorized based on the 2020 World Health Organization classification system.ResultsPatients diagnosed with bone sarcomas were significantly younger than those diagnosed with STS (p < 0.01). The top 10 frequently altered genes in bone sarcoma and STS were TP53, CDKN2A, CDKN2B, MAP3K1, LRP1B, MDM2, RB1, PTEN, MYC, and CDK4.The EWSR1 fusions exhibited statistically significant differences (p < 0.01) between primary bone sarcoma and STS in terms of their altered genes. Based on the actionable genes defined by OncoKB, actionable GAs was found in 30.7% (23/75) of the patients with bone sarcomas and 35.7% (25/70) of those with STS. There were 4.0% (3/75) patients with bone sarcoma and 4.3% (3/70) patients with STS exhibited high tumor mutational burden (TMB-H) (TMB ≥ 10). There was only one patient with STS exhibited MSI-L, while the remaining cases were microsatellite stable. The positive rate of PD-L1 expression was slightly higher in STS (35.2%) than in bone sarcoma (33.3%), however, this difference did not reach statistical significance. The expression of PD-L1 in STS patients was associated with a poorer prognosis (p = 0.007). Patients with STS had a better prognosis than those with bone sarcoma, but the observed difference did not attain statistical significance (p = 0.21). Amplification of MET and MYC genes were negatively correlated with clinical prognosis in bone tumors (p<0.01).DiscussionIn conclusion, bone sarcoma and STS have significantly different clinical and molecular characteristics, suggesting that it is vital to diagnose accurately for clinical treatment. Additionally, comprehensive genetic landscape can provide novel treatment perspectives for primary bone sarcoma and STS. Taking TMB, MSI, PD-L1 expression, and OncoKB definition together into consideration, there are still many patients who have the potential to respond to targeted therapy or immunotherapy. |
| first_indexed | 2024-03-12T22:28:25Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T22:28:25Z |
| publishDate | 2023-07-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-2623aa890a5d448cb872e3df1890022a2023-07-21T18:45:55ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-07-011310.3389/fonc.2023.11732751173275Comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomasQing Zhang0Yongkun Yang1Xia You2Xia You3Xia You4Yongzhi Ju5Yongzhi Ju6Yongzhi Ju7Qin Zhang8Qin Zhang9Qin Zhang10Tingting Sun11Tingting Sun12Tingting Sun13Weifeng Liu14Department of Orthopaedic Oncology, Beijing Ji Shui Tan Hospital, Peking University, Beijing, ChinaDepartment of Orthopaedic Oncology, Beijing Ji Shui Tan Hospital, Peking University, Beijing, ChinaThe Medical Department, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, ChinaNanjing Simcere Medical Laboratory Science Co., Ltd, Nanjing, Jiangsu, ChinaThe State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, ChinaThe Medical Department, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, ChinaNanjing Simcere Medical Laboratory Science Co., Ltd, Nanjing, Jiangsu, ChinaThe State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, ChinaThe Medical Department, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, ChinaNanjing Simcere Medical Laboratory Science Co., Ltd, Nanjing, Jiangsu, ChinaThe State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, ChinaThe Medical Department, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, ChinaNanjing Simcere Medical Laboratory Science Co., Ltd, Nanjing, Jiangsu, ChinaThe State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, ChinaDepartment of Orthopaedic Oncology, Beijing Ji Shui Tan Hospital, Peking University, Beijing, ChinaIntroductionSarcomas are classified into two types, bone sarcoma and soft tissue sarcoma (STS), which account for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. There exist more than 50 subtypes within the two types of sarcoma. Each subtype is highly diverse and characterized by significant variations in morphology and phenotypes. Understanding tumor molecular genetics is helpful in improving the diagnostic accuracy of tumors that have been difficult to classify based on morphology alone or that have overlapping morphological features. The different molecular characteristics of bone sarcoma and STS in China remain poorly understood. Therefore, this study aimed to analyze genomic landscapes and actionable genomic alterations (GAs) as well as tumor mutational burden (TMB), microsatellite instability (MSI), and programmed death ligand-1 (PD-L1) expression among Chinese individuals diagnosed with primary bone sarcomas and STS.MethodsThis retrospective study included 145 patients with primary bone sarcomas (n = 75) and STS (n = 70), who were categorized based on the 2020 World Health Organization classification system.ResultsPatients diagnosed with bone sarcomas were significantly younger than those diagnosed with STS (p < 0.01). The top 10 frequently altered genes in bone sarcoma and STS were TP53, CDKN2A, CDKN2B, MAP3K1, LRP1B, MDM2, RB1, PTEN, MYC, and CDK4.The EWSR1 fusions exhibited statistically significant differences (p < 0.01) between primary bone sarcoma and STS in terms of their altered genes. Based on the actionable genes defined by OncoKB, actionable GAs was found in 30.7% (23/75) of the patients with bone sarcomas and 35.7% (25/70) of those with STS. There were 4.0% (3/75) patients with bone sarcoma and 4.3% (3/70) patients with STS exhibited high tumor mutational burden (TMB-H) (TMB ≥ 10). There was only one patient with STS exhibited MSI-L, while the remaining cases were microsatellite stable. The positive rate of PD-L1 expression was slightly higher in STS (35.2%) than in bone sarcoma (33.3%), however, this difference did not reach statistical significance. The expression of PD-L1 in STS patients was associated with a poorer prognosis (p = 0.007). Patients with STS had a better prognosis than those with bone sarcoma, but the observed difference did not attain statistical significance (p = 0.21). Amplification of MET and MYC genes were negatively correlated with clinical prognosis in bone tumors (p<0.01).DiscussionIn conclusion, bone sarcoma and STS have significantly different clinical and molecular characteristics, suggesting that it is vital to diagnose accurately for clinical treatment. Additionally, comprehensive genetic landscape can provide novel treatment perspectives for primary bone sarcoma and STS. Taking TMB, MSI, PD-L1 expression, and OncoKB definition together into consideration, there are still many patients who have the potential to respond to targeted therapy or immunotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2023.1173275/fullsarcomamutation profilemicrosatellite instabilitytherapeutic gene alterationtumor mutation burdenPD-L1 |
| spellingShingle | Qing Zhang Yongkun Yang Xia You Xia You Xia You Yongzhi Ju Yongzhi Ju Yongzhi Ju Qin Zhang Qin Zhang Qin Zhang Tingting Sun Tingting Sun Tingting Sun Weifeng Liu Comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomas Frontiers in Oncology sarcoma mutation profile microsatellite instability therapeutic gene alteration tumor mutation burden PD-L1 |
| title | Comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomas |
| title_full | Comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomas |
| title_fullStr | Comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomas |
| title_full_unstemmed | Comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomas |
| title_short | Comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomas |
| title_sort | comprehensive genomic analysis of primary bone sarcomas reveals different genetic patterns compared with soft tissue sarcomas |
| topic | sarcoma mutation profile microsatellite instability therapeutic gene alteration tumor mutation burden PD-L1 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1173275/full |
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