Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence
Abstract Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challen...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-023-00453-1 |
| _version_ | 1827725010398085120 |
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| author | Jinsen Zhang Yuan Feng Guanghao Li Jianhua Zhang Xin Zhang Yi Zhang Zhiyong Qin Dongxiao Zhuang Tianming Qiu Zhifeng Shi Wei Zhu Rui Zhang Yonghe Wu Haikun Liu Dandan Cao Wei Hua Ying Mao |
| author_facet | Jinsen Zhang Yuan Feng Guanghao Li Jianhua Zhang Xin Zhang Yi Zhang Zhiyong Qin Dongxiao Zhuang Tianming Qiu Zhifeng Shi Wei Zhu Rui Zhang Yonghe Wu Haikun Liu Dandan Cao Wei Hua Ying Mao |
| author_sort | Jinsen Zhang |
| collection | DOAJ |
| description | Abstract Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P < 0.05). Further, patients with acquired gains of 1q, 6p or loss of 13q at recurrence had a shorter overall survival in lower grade astrocytoma (P < 0.05); however, these prognostic effects were confined in grade 4 astrocytoma and GB. Moreover, acquired gains of 12 genes (including VEGFA) on 6p during relapse were associated with unfavorable prognosis for lower grade astrocytoma patients. Notably, elevated VEGFA expression during recurrence corresponded to poorer survival, validated through IHC and CGGA data. To summarize, these findings offer valuable insights into the progression of gliomas and have implications for guiding therapeutic approaches during recurrence. |
| first_indexed | 2024-03-10T22:22:27Z |
| format | Article |
| id | doaj.art-a46094dd4ac44daf83aa303bff56891b |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-10T22:22:27Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-a46094dd4ac44daf83aa303bff56891b2023-11-19T12:14:04ZengNature Portfolionpj Precision Oncology2397-768X2023-09-017111010.1038/s41698-023-00453-1Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrenceJinsen Zhang0Yuan Feng1Guanghao Li2Jianhua Zhang3Xin Zhang4Yi Zhang5Zhiyong Qin6Dongxiao Zhuang7Tianming Qiu8Zhifeng Shi9Wei Zhu10Rui Zhang11Yonghe Wu12Haikun Liu13Dandan Cao14Wei Hua15Ying Mao16Department of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityGenetron Health (Beijing) Co. Ltd.Genetron Health (Beijing) Co. Ltd.Department 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 Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityShanghai KR Pharmtech, Inc., LtdShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityGenetron Health (Beijing) Co. Ltd.Department of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityAbstract Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P < 0.05). Further, patients with acquired gains of 1q, 6p or loss of 13q at recurrence had a shorter overall survival in lower grade astrocytoma (P < 0.05); however, these prognostic effects were confined in grade 4 astrocytoma and GB. Moreover, acquired gains of 12 genes (including VEGFA) on 6p during relapse were associated with unfavorable prognosis for lower grade astrocytoma patients. Notably, elevated VEGFA expression during recurrence corresponded to poorer survival, validated through IHC and CGGA data. To summarize, these findings offer valuable insights into the progression of gliomas and have implications for guiding therapeutic approaches during recurrence.https://doi.org/10.1038/s41698-023-00453-1 |
| spellingShingle | Jinsen Zhang Yuan Feng Guanghao Li Jianhua Zhang Xin Zhang Yi Zhang Zhiyong Qin Dongxiao Zhuang Tianming Qiu Zhifeng Shi Wei Zhu Rui Zhang Yonghe Wu Haikun Liu Dandan Cao Wei Hua Ying Mao Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence npj Precision Oncology |
| title | Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence |
| title_full | Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence |
| title_fullStr | Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence |
| title_full_unstemmed | Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence |
| title_short | Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence |
| title_sort | distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence |
| url | https://doi.org/10.1038/s41698-023-00453-1 |
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