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Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients

BACKGROUND: Soft‐tissue sarcoma (STS) is a rare solid malignant tumor with numerous histologic subtypes. Current studies on targeted therapy for STS are in preclinical and early‐phase trials. Genomic differences largely influence the prognosis of patients even with the same subtype. To investigate t...

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Autores principales: Gan, Meifu, Zhang, Chen, Qiu, Liqing, Wang, Yue, Bao, Hua, Yu, Ruoying, Liu, Rui, Wu, Xue, Shao, Yang, Hou, Peifeng, Fei, Zhenglei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636498/
https://www.ncbi.nlm.nih.gov/pubmed/35586877
http://dx.doi.org/10.1002/cam4.4725
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author Gan, Meifu
Zhang, Chen
Qiu, Liqing
Wang, Yue
Bao, Hua
Yu, Ruoying
Liu, Rui
Wu, Xue
Shao, Yang
Hou, Peifeng
Fei, Zhenglei
author_facet Gan, Meifu
Zhang, Chen
Qiu, Liqing
Wang, Yue
Bao, Hua
Yu, Ruoying
Liu, Rui
Wu, Xue
Shao, Yang
Hou, Peifeng
Fei, Zhenglei
author_sort Gan, Meifu
collection PubMed
description BACKGROUND: Soft‐tissue sarcoma (STS) is a rare solid malignant tumor with numerous histologic subtypes. Current studies on targeted therapy for STS are in preclinical and early‐phase trials. Genomic differences largely influence the prognosis of patients even with the same subtype. To investigate the genomic alterations (GAs) and the potential of targeted therapy in STS, we analyzed the genomic landscape, the therapeutic GAs, and biomarkers of immunotherapy in Chinese STS patients. METHODS: Targeted sequencing covering 425 genes was performed, from which we obtained the results of tissue samples from 351 Chinese STS patients of all ages covering different histologic subtypes. Bioinformatics analysis of altered genes with nonsynonymous mutations, copy‐number variations, and gene fusions were performed. OncoKB therapeutic GAs and relevant biomarkers including TMB, MSI, and HRD were further examined for potential targeted therapy. RESULTS: In total, 2743 GAs were identified in 330 genes with a median of 6 (1–38) per case. The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1. OncoKB defined therapeutic GAs were found in 23 genes in 43% of the patients. In general, 9.4% of the patients had high‐TMB, 2.8% had MSI, and 13.7% had HRD. A significant difference in the percentage of patients with OncoKB therapeutic GAs were observed between the most frequent two subtypes, leiomyosarcoma and liposarcoma. Altogether, 54% of the patients had the potential to respond to a targeted therapy. CONCLUSION: This study indicated the potential efficacy of targeted therapy on many STS patients, and also provided insight for novel precision therapy. The clinical efficacy of combining targeted therapy and immunotherapy can be further investigated.
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spelling pubmed-96364982022-11-07 Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients Gan, Meifu Zhang, Chen Qiu, Liqing Wang, Yue Bao, Hua Yu, Ruoying Liu, Rui Wu, Xue Shao, Yang Hou, Peifeng Fei, Zhenglei Cancer Med Research Article BACKGROUND: Soft‐tissue sarcoma (STS) is a rare solid malignant tumor with numerous histologic subtypes. Current studies on targeted therapy for STS are in preclinical and early‐phase trials. Genomic differences largely influence the prognosis of patients even with the same subtype. To investigate the genomic alterations (GAs) and the potential of targeted therapy in STS, we analyzed the genomic landscape, the therapeutic GAs, and biomarkers of immunotherapy in Chinese STS patients. METHODS: Targeted sequencing covering 425 genes was performed, from which we obtained the results of tissue samples from 351 Chinese STS patients of all ages covering different histologic subtypes. Bioinformatics analysis of altered genes with nonsynonymous mutations, copy‐number variations, and gene fusions were performed. OncoKB therapeutic GAs and relevant biomarkers including TMB, MSI, and HRD were further examined for potential targeted therapy. RESULTS: In total, 2743 GAs were identified in 330 genes with a median of 6 (1–38) per case. The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1. OncoKB defined therapeutic GAs were found in 23 genes in 43% of the patients. In general, 9.4% of the patients had high‐TMB, 2.8% had MSI, and 13.7% had HRD. A significant difference in the percentage of patients with OncoKB therapeutic GAs were observed between the most frequent two subtypes, leiomyosarcoma and liposarcoma. Altogether, 54% of the patients had the potential to respond to a targeted therapy. CONCLUSION: This study indicated the potential efficacy of targeted therapy on many STS patients, and also provided insight for novel precision therapy. The clinical efficacy of combining targeted therapy and immunotherapy can be further investigated. John Wiley and Sons Inc. 2022-05-18 /pmc/articles/PMC9636498/ /pubmed/35586877 http://dx.doi.org/10.1002/cam4.4725 Text en © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Gan, Meifu
Zhang, Chen
Qiu, Liqing
Wang, Yue
Bao, Hua
Yu, Ruoying
Liu, Rui
Wu, Xue
Shao, Yang
Hou, Peifeng
Fei, Zhenglei
Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients
title Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients
title_full Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients
title_fullStr Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients
title_full_unstemmed Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients
title_short Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients
title_sort molecular landscape and therapeutic alterations in asian soft‐tissue sarcoma patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636498/
https://www.ncbi.nlm.nih.gov/pubmed/35586877
http://dx.doi.org/10.1002/cam4.4725
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