Tumor Biology Research Program, Basic Research Unit, Research Department, Children's Cancer Hospital Egypt 57357, 1 Sekket El Emam, El Madbah El Kadeem Yard, Sayeda Zeinab, Cairo, Egypt.
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
J Neurooncol. 2024 Jan;166(1):27-38. doi: 10.1007/s11060-023-04484-3. Epub 2024 Jan 8.
Choroid plexus carcinomas (CPCs) are extremely rare brain tumors and carry a dismal prognosis. Treatment options are limited and there is an urgent need to develop models to further research. In the present study, we established two CPC cell lines and performed multi-omics analyses. These cell lines serve as valuable models to propose new treatments in these rare but deadly brain tumors.
Multi-omic profiling including, (i) methylation array (EPIC 850 K), (ii) whole genome sequencing (WGS), (iii) CANCERPLEX cancer genome panel testing, (iv) RNA sequencing (RNA-seq), and (v) proteomics analyses were performed in CCHE-45 and NGT131 cell lines.
Both cell lines were classified as methylation class B. Both harbored pathogenic TP53 point mutations; CCHE-45 additionally displayed TP53 loss. Furthermore, alterations of the NOTCH and WNT pathways were also detected in both cell lines. Two protein-coding gene fusions, BZW2-URGCP, and CTTNBP2-ERBB4, mutations of two oncodrivers, GBP-4 and KRTAP-12-2, and several copy number alterations were observed in CCHE-45, but not NGT131. Transcriptome and proteome analysis identified shared and unique signatures, suggesting that variability in choroid plexus carcinoma tumors may exist. The discovered difference's importance and implications highlight the possible diversity of choroid plexus carcinoma and call for additional research to fully understand disease pathogenesis.
Multi-omics analyses revealed that the two choroid plexus carcinoma cell lines shared TP53 mutations and other common pathway alterations and activation of NOTCH and WNT pathways. Noticeable differences were also observed. These cell lines can serve as valuable models to propose new treatments in these rare but deadly brain tumors.
脉络丛癌（CPC）是一种极为罕见的脑肿瘤，预后极差。治疗选择有限，因此迫切需要建立模型以进一步开展研究。本研究建立了两种 CPC 细胞系，并进行了多组学分析。这些细胞系可作为有价值的模型，为这些罕见但致命的脑肿瘤提出新的治疗方法。
对 CCHE-45 和 NGT131 细胞系进行多组学分析，包括（i）甲基化芯片（EPIC 850K），（ii）全基因组测序（WGS），（iii）CANCERPLEX 癌症基因组面板检测，（iv）RNA 测序（RNA-seq）和（v）蛋白质组学分析。
两种细胞系均被归类为甲基化 B 类。两种细胞均携带致病性 TP53 点突变；CCHE-45 还显示 TP53 缺失。此外，两种细胞系均检测到 NOTCH 和 WNT 通路的改变。在 CCHE-45 中观察到两种蛋白编码基因融合，BZW2-URGCP 和 CTTNBP2-ERBB4，两种癌基因驱动突变，GBP-4 和 KRTAP-12-2，以及几个拷贝数改变，但 NGT131 中未观察到。转录组和蛋白质组分析鉴定了共享和独特的特征，表明脉络丛癌肿瘤可能存在变异性。发现的差异的重要性和意义突出了脉络丛癌的可能多样性，并呼吁进一步研究以充分了解疾病的发病机制。
多组学分析表明，两种脉络丛癌细胞系共享 TP53 突变和其他常见的通路改变以及 NOTCH 和 WNT 通路的激活。还观察到明显的差异。这些细胞系可作为有价值的模型，为这些罕见但致命的脑肿瘤提出新的治疗方法。
