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Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma
AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcoma...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611784/ https://www.ncbi.nlm.nih.gov/pubmed/34605602 http://dx.doi.org/10.1111/cns.13740 |
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author | Li, Jie Zhao, Yu‐Hang Tian, Su‐Fang Xu, Cheng‐Shi Cai, Yu‐Xiang Li, Kai Cheng, Yan‐Bing Wang, Ze‐Fen Li, Zhi‐Qiang |
author_facet | Li, Jie Zhao, Yu‐Hang Tian, Su‐Fang Xu, Cheng‐Shi Cai, Yu‐Xiang Li, Kai Cheng, Yan‐Bing Wang, Ze‐Fen Li, Zhi‐Qiang |
author_sort | Li, Jie |
collection | PubMed |
description | AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post‐radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole‐genome sequencing and deep‐whole‐exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor‐suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating‐agents – exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS. |
format | Online Article Text |
id | pubmed-8611784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86117842021-11-30 Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma Li, Jie Zhao, Yu‐Hang Tian, Su‐Fang Xu, Cheng‐Shi Cai, Yu‐Xiang Li, Kai Cheng, Yan‐Bing Wang, Ze‐Fen Li, Zhi‐Qiang CNS Neurosci Ther Original Articles AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post‐radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole‐genome sequencing and deep‐whole‐exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor‐suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating‐agents – exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS. John Wiley and Sons Inc. 2021-10-04 /pmc/articles/PMC8611784/ /pubmed/34605602 http://dx.doi.org/10.1111/cns.13740 Text en © 2021 The Authors. CNS Neuroscience & Therapeutics 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 | Original Articles Li, Jie Zhao, Yu‐Hang Tian, Su‐Fang Xu, Cheng‐Shi Cai, Yu‐Xiang Li, Kai Cheng, Yan‐Bing Wang, Ze‐Fen Li, Zhi‐Qiang Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma |
title | Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma |
title_full | Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma |
title_fullStr | Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma |
title_full_unstemmed | Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma |
title_short | Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma |
title_sort | genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611784/ https://www.ncbi.nlm.nih.gov/pubmed/34605602 http://dx.doi.org/10.1111/cns.13740 |
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