IDH clonal heterogeneity segregates a subgroup of non-1p/19q codeleted gliomas with unfavourable clinical outcome
| Autor: | Yun Xiao, Shangyi Luo, Jinyuan Xu, Tao Luo, Shiwei Zhu, Xia Li, Xiaobo Hou, Lin Pang, Jianlong Liao, Yajing Zhang, Erjie Zhao, Xin Liang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Histology IDH1 Adolescent Somatic cell Biology World health Pathology and Forensic Medicine 03 medical and health sciences Diffuse Glioma Young Adult 0302 clinical medicine Molecular classification Physiology (medical) Glioma medicine Cluster Analysis Humans Gene Aged Genetics Aged 80 and over Brain Neoplasms Clinical course Middle Aged medicine.disease Prognosis Isocitrate Dehydrogenase 030104 developmental biology Neurology Mutation Female Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Neuropathology and applied neurobiologyREFERENCES. 47(3) |
| ISSN: | 1365-2990 |
| Popis: | Aims Diffuse gliomas (DGs) are classified into three major molecular subgroups following the revised World Health Organisation (WHO) classification criteria based on their IDH mutation and 1p/19q codeletion status. However, substantial biological heterogeneity and differences in the clinical course are apparent within each subgroup, which remain to be resolved. We sought to assess the clonal status of somatic mutations and explore whether additional molecular subgroups exist within DG. Methods A computational framework that integrates the variant allele frequency, local copy number and tumour purity was used to infer the clonality of somatic mutations in 876 DGs from The Cancer Genome Atlas (TCGA). We performed an unsupervised cluster analysis to identify molecular subgroups and characterised their clinical and biological significance. Results DGs showed widespread genetic intratumoural heterogeneity (ITH), with nearly all driver genes harbouring subclonal mutations, even for known glioma initiating event IDH1 (17.1%). Gliomas with subclonal IDH mutation and without 1p/19q codeletion showed shorter overall and disease-specific survival, higher ITH and exhibited differences in genomic patterns, transcript levels and proliferative potential, when compared with IDH clonal mutation and no 1p/19q codeletion gliomas. We defined a refined stratification system based on the current WHO glioma molecular classification, which showed close correlations with patients' clinical outcomes. Conclusions For the first time, we integrated the clonal status of somatic mutations into cancer genomic classification and highlighted the necessity of considering IDH clonal architectures in glioma precision stratification. |
| Databáze: | OpenAIRE |
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