Chen Chia-Hua, Lin Ya-Jui, Lin You-Yu, Lin Chang-Hung, Feng Li-Ying, Chang Ian Yi-Feng, Wei Kuo-Chen, Huang Chiung-Yin
Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
Front Oncol. 2021 Apr 26;11:621432. doi: 10.3389/fonc.2021.621432. eCollection 2021.
Gliomas are solid tumors that originate from glial cells in the brain or spine and account for 74.6% of malignant primary central nervous system tumors worldwide. As patient-derived primary cells are important tools for drug screening and new therapy development in glioma, we aim to understand the genomic similarity of the primary cells to their parental tumors by comparing their whole-genome copy number variations and expression profile of glioma clinicopathologic factors. We found that the primary cells from grade II/III gliomas lost most of the gene copy number alterations (CNAs), which were mainly located on chromosome 1p and 19q in their parental tumors. The glioblastoma (GBM) primary cells preserved 83.7% of the gene CNAs in the parental GBM tumors, including chromosome 7 gain and 10q loss. The CNA gains of and and the chromosome 16p11 loss were reconstituted in primary cells from both grade II/III gliomas and GBMs. Interestingly, we found these CNAs were correlated to overall survival (OS) in glioma patients using the Merged Cohort LGG and GBM dataset from cBioPortal. The gene CNAs preserved in glioma primary cells often predicted poor survival, whereas the gene CNAs lost in grade II/III primary cells were mainly associated to better prognosis in glioma patients. Glioma prognostic factors that predict better survival, such as mutations and 1p/19q codeletion in grade II/III gliomas, were lost in their primary cells, whereas methylated promoters as well as promoter mutations were preserved in GBM primary cells while lost in grade II/III primary cells. Our results suggest that GBM primary cells tend to preserve CNAs in their parental tumors, and these CNAs are correlated to poor OS and predict worse prognosis in glioma patients.
胶质瘤是起源于脑或脊髓神经胶质细胞的实体瘤，占全球原发性中枢神经系统恶性肿瘤的74.6%。由于患者来源的原代细胞是胶质瘤药物筛选和新疗法开发的重要工具，我们旨在通过比较胶质瘤临床病理因素的全基因组拷贝数变异和表达谱，了解原代细胞与其亲本肿瘤的基因组相似性。我们发现，II/III级胶质瘤的原代细胞失去了大部分基因拷贝数改变（CNA），这些改变主要位于其亲本肿瘤的1号染色体短臂和19号染色体长臂。胶质母细胞瘤（GBM）原代细胞保留了亲本GBM肿瘤中83.7%的基因CNA，包括7号染色体增益和10号染色体长臂缺失。II/III级胶质瘤和GBM的原代细胞中都重新出现了 和 的CNA增益以及16号染色体短臂11区缺失。有趣的是，我们使用来自cBioPortal的合并队列低级别胶质瘤（LGG）和GBM数据集发现，这些CNA与胶质瘤患者的总生存期（OS）相关。胶质瘤原代细胞中保留的基因CNA通常预示着较差的生存率，而II/III级原代细胞中丢失的基因CNA主要与胶质瘤患者较好的预后相关。预测更好生存率的胶质瘤预后因素，如II/III级胶质瘤中的 突变和1p/19q共缺失，在其原代细胞中丢失，而甲基化的 启动子以及 启动子突变在GBM原代细胞中保留，而在II/III级原代细胞中丢失。我们的结果表明，GBM原代细胞倾向于保留其亲本肿瘤中的CNA，这些CNA与较差的OS相关，并预示着胶质瘤患者更差的预后。
