Comprehensive molecular characterization of adult H3K27M mutated thalamic glioma long-term survivors
Abstract H3K27-altered diffuse midline gliomas (H3-DMGs) represent aggressive tumors with fatal outcome and exceedingly rare cases have a long-term survival (LTS). We included 5 adult thalamic H3-DMG LTS and 13 short-term survivors (STS), and performed whole exome sequencing, RNA-seq and DNA methyla...
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BMC
2025-06-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s40164-025-00677-w |
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| author | Hao Xu Xiaomu Hu Biyun Wang Ying Sun Ye Wang Qisheng Tang Qiongji Zhu Kun Song Hong Chen Lingchao Chen Haixia Cheng Zhiyong Qin |
| author_facet | Hao Xu Xiaomu Hu Biyun Wang Ying Sun Ye Wang Qisheng Tang Qiongji Zhu Kun Song Hong Chen Lingchao Chen Haixia Cheng Zhiyong Qin |
| author_sort | Hao Xu |
| collection | DOAJ |
| description | Abstract H3K27-altered diffuse midline gliomas (H3-DMGs) represent aggressive tumors with fatal outcome and exceedingly rare cases have a long-term survival (LTS). We included 5 adult thalamic H3-DMG LTS and 13 short-term survivors (STS), and performed whole exome sequencing, RNA-seq and DNA methylation array. The median overall survival was 48.0 ± 12.1 months for LTS and 12.5 ± 5.9 months for STS. There was no significant difference in clinical characteristics and treatment received between LTS and STS. LTS exhibited more copy number gain and amplification (P = 0.007), and tumor microenvironment analysis revealed increased accumulation of M1 macrophage (P = 0.005) alongside a notable reduction in cancer-associated fibroblast in LTS (P = 0.037). The signatures of LTS and STS were signature 30 (similarity = 76.7%) and signature 6 (81.8%), respectively. Of note, LTS exhibited hypermethylated CpG island (P = 0.002). Additionally, we demonstrated that LTS and STS could be distinguished using differentially methylated probes. Collectively, the present study delineated unique molecular characteristics of LTS H3-DMG. |
| format | Article |
| id | doaj-art-7749ba4b04ef4716be75c2e484c3d0e3 |
| institution | DOAJ |
| issn | 2162-3619 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj-art-7749ba4b04ef4716be75c2e484c3d0e32025-08-20T02:40:15ZengBMCExperimental Hematology & Oncology2162-36192025-06-011411610.1186/s40164-025-00677-wComprehensive molecular characterization of adult H3K27M mutated thalamic glioma long-term survivorsHao Xu0Xiaomu Hu1Biyun Wang2Ying Sun3Ye Wang4Qisheng Tang5Qiongji Zhu6Kun Song7Hong Chen8Lingchao Chen9Haixia Cheng10Zhiyong Qin11Department of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Nursing, Huashan Hospital, Fudan UniversityGenomiCare Biotechnology (Shanghai) Co. LtdDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityAbstract H3K27-altered diffuse midline gliomas (H3-DMGs) represent aggressive tumors with fatal outcome and exceedingly rare cases have a long-term survival (LTS). We included 5 adult thalamic H3-DMG LTS and 13 short-term survivors (STS), and performed whole exome sequencing, RNA-seq and DNA methylation array. The median overall survival was 48.0 ± 12.1 months for LTS and 12.5 ± 5.9 months for STS. There was no significant difference in clinical characteristics and treatment received between LTS and STS. LTS exhibited more copy number gain and amplification (P = 0.007), and tumor microenvironment analysis revealed increased accumulation of M1 macrophage (P = 0.005) alongside a notable reduction in cancer-associated fibroblast in LTS (P = 0.037). The signatures of LTS and STS were signature 30 (similarity = 76.7%) and signature 6 (81.8%), respectively. Of note, LTS exhibited hypermethylated CpG island (P = 0.002). Additionally, we demonstrated that LTS and STS could be distinguished using differentially methylated probes. Collectively, the present study delineated unique molecular characteristics of LTS H3-DMG.https://doi.org/10.1186/s40164-025-00677-wH3K27-altered diffuse midline gliomaLong-term survivorMutation analysisRNA sequencingDNA methylation array |
| spellingShingle | Hao Xu Xiaomu Hu Biyun Wang Ying Sun Ye Wang Qisheng Tang Qiongji Zhu Kun Song Hong Chen Lingchao Chen Haixia Cheng Zhiyong Qin Comprehensive molecular characterization of adult H3K27M mutated thalamic glioma long-term survivors Experimental Hematology & Oncology H3K27-altered diffuse midline glioma Long-term survivor Mutation analysis RNA sequencing DNA methylation array |
| title | Comprehensive molecular characterization of adult H3K27M mutated thalamic glioma long-term survivors |
| title_full | Comprehensive molecular characterization of adult H3K27M mutated thalamic glioma long-term survivors |
| title_fullStr | Comprehensive molecular characterization of adult H3K27M mutated thalamic glioma long-term survivors |
| title_full_unstemmed | Comprehensive molecular characterization of adult H3K27M mutated thalamic glioma long-term survivors |
| title_short | Comprehensive molecular characterization of adult H3K27M mutated thalamic glioma long-term survivors |
| title_sort | comprehensive molecular characterization of adult h3k27m mutated thalamic glioma long term survivors |
| topic | H3K27-altered diffuse midline glioma Long-term survivor Mutation analysis RNA sequencing DNA methylation array |
| url | https://doi.org/10.1186/s40164-025-00677-w |
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